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All issues Volume 3 / No 6 (2024) Natl Sci Open, 3 6 (2024) 20240042 Full HTML
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Natl Sci Open
Volume 3, Number 6, 2024
Special Topic: Key Materials for Carbon Neutrality
Article Number 20240042
Number of page(s) 32
Section Materials Science
DOI https://doi.org/10.1360/nso/20240042
Published online 22 October 2024

© The Author(s) 2024. Published by Science Press and EDP Sciences.

Licence Creative CommonsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

INTRODUCTION

Due to their high frequency of occurrence and deadly outcomes, cancer remains among the most critical and challenging health issues faced by humans [1–3]. Standard medical interventions for cancer, including conventional chemotherapy and radiation therapy, often lead to the emergence of resistance to treatment and considerable harm to healthy tissues [4–6]. Over the past few decades, a variety of nanomaterials have been employed as vehicles for delivering cancer-fighting agents. These encompass polymers, liposomes, micelles, solid lipid nanoparticles (NPs), quantum dots, dendritic materials, as well as noble metal NPs [7–9]. However, the aforementioned nanomaterials have limitations such as restricted drug delivery rate, significant cytotoxicity and inadequate biocompatibility [10–12]. The satisfactory nanomaterials used for drug delivery generally possess characteristics of multilayers, mesoporosity, hollowness, etc. with unique nano-size, adjustable pore structure and good biocompatibility, making them preferred nanomaterials for drug carriers [13–15]. Organic frameworks, a type of poriferous materials with a crystalline structure, have gained increasingly prominent over the years. These frameworks, composed of metal and covalent bonds, have attracted considerable interest due to their potential in tumor therapy. Their benefits include biocompatibility, an elevated surface-to-volume ratio, and the capacity for easy functionalization [16–19].

Covalent organic frameworks (COFs) are composed of porous structures or covalent crystalline polymers that form precise atomic-level structures through the linking organic networks [20–22]. Yaghi and his colleagues first presented this category of materials in 2005 [23]. Subsequent advancements have been accounts of COFs linked with B–O, C=N, C=C, and various other bond types [24]. COFs can be produced by connecting different organic monomers through various syntheses methods, including solvothermal, sonochemical, ionothermal, mechanochemical, and light-assisted synthesis [25–27]. COFs can be classified as either 2D COFs or 3D COFs depending on their particular structure [28–31]. It should be noted that porous crystals, whether 2D or 3D, possess a distinctive spatial arrangement of subunits, which grants them an array of highly sought-after properties [32]. These include a reduced density, a wide variety of structural forms, a porous framework, a large specific surface area, the absence of heavy metals ions, and the ability to adjust the pore size [33–35].

After being specifically modified, the application of COFs has been expanded in the fields of drug delivery and cancer treatment [36–38]. The prime benefits of COFs are predominantly showcased through the following dimensions: (1) Owing to their unique architectural features, COFs are highly susceptible to modifications, enabling their utility in biomedical contexts such as cancer cell targeting, fluorescence-based imaging, and malignancy treatment modalities. (2) Their inherent porosity allows COFs to incorporate foreign molecules within their cavities, making them suitable as carriers for pharmaceutical delivery systems. (3) Due to their conjugated nature, the building blocks of COFs possess distinct energy level configurations within the matrix. (4) The metal ion-free composition of COFs helps to alleviate potential biological toxicity issues associated with metallic elements [39–42]. Consequently, COFs have been the focus of recent research as potential nanoplatforms for treating cancer due to their distinct properties [43–45]. They have the capability to transport chemotherapy drugs, biomolecules, photosensitizers, and/or photothermal agents [10,46–48].

Here, we classify the use of COFs in cancer treatment into five categories: chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy and combination therapy [49–51]. Each COF is subjected to target cells to evaluate their effects in the applications of these therapies. The morphology of COFs determines the degree of interaction between COFs and cells [52–55]. As a biomaterial, the biocompatibility of COFs is also an important issue that must be considered. Biocompatibility refers to the ability of a material to elicit a biological response and be completely cleared from the body without causing unacceptable toxicity [56]. The later phase of biocompatibility is achieved when the material does not cause unacceptable toxic, carcinogenic, or immunogenic reactions [57]. Therefore, to evaluate biocompatibility, it is important to carefully assess the physical properties of the nanoparticles to predict how they may interact with blood and cell organelles. Since the use of COFs for theranostic purposes is still in its early stages and there is limited information available on their long-term biocompatibility, in this review, we focus on the application of COFs morphologies in tumor therapy.

In this review, we explicitly discuss COFs with different morphologies in theranostic applications. The main morphologies of COFs for treating tumors can be categorized into four categories as shown in Fig. 1: nanospheres, nanosheets, nano-rods/tubes and nanoparticles [58–61]. Moreover, we review recent research articles and systematically discuss recent advances in COFs in chemotherapy, chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT) and combination therapy (as shown in Fig. 1). Furthermore, the development and utilization of COFs are at an early stage and there are many challenges [62–64]. The intrinsic constraints of COFs, including inadequate biostability, challenges in dispersion, and the lack of specificity in targeting, restrict their utility in cancer treatment applications [65–68]. In conclusion, we will explore the potential prospects and obstacles facing COFs in oncology therapy and aim to inspire researchers to develop more efficient and stable COFs materials.

thumbnail Figure 1

Schematic illustration of the topics involved in the review.

MORPHOLOGY OF COFS IN TUMOR THERAPY

The morphology of COFs plays a crucial role in tumor therapy, which will affect the biocompatibility of COFs [69–73]. Various forms of cell uptake, including nanospheres, nanosheets, nanotubes and nanocapsules have been used in tumor therapy [74–77]. For example, the cellular uptake of spherical nanoparticles was observed to be faster than that of nanorods, possibly due to the reduced tendency for aggregation in spherical nanoparticles [78]. Consequently, for achieving more precision in tumor therapy, the thorough investigation of the correlation between the morphology of COFs and therapeutic efficacy has become an essential prerequisite. Table 1 presents an overview of the morphological characteristics of COFs discussed in this review and relation to their potential applications in anticancer research.

Table 1

Summary of recent studies in nanosystems on base of COFs with different morphologies for anticancer applications

Nanospheres COFs

As mentioned above, the absorption rate of spherical nanoparticles is faster than that of other morphologies, not only because of the lower aggregation rate, but also because of the larger specific surface area [42,108–111]. Therefore, there have been numerous studies on the use of nanospheres COFs in tumor therapy [112–114]. In 2022, Wang’s research team transformed porphyrin COF (P-COF) into nanospheres that were compatible with various imine COFs [85]. As shown in Fig. 2a, the Fe3+ was then coordinated to the porphyrin unit. By utilizing a layer of PLG-g-mPEG, PgP@Fe-COF NPs exhibited an orderly distribution of porphyrin molecules and improved stability of the structure. The FT-IR curve revealed the successful preparation of PgP@Fe-COF NPs (Fig. 2b), and DLS analysis indicated a particle size of approximately 160 nm (Fig. 2c). As a result, the nanosized sonosensitizer (PgP@Fe-COF NPs) exhibited excellent properties in sonodynamic therapy (Fig. 2d). This sonosensitizer exhibited CDT efficacy via the Fenton reaction and improved its capacity to destroy tumors by depleting glutathione. Additionally, Chen documented the synthesis of two nanospheres of COFs based on CDs (referred to as CCOF-1 and CCOF-2) in 2020 [90]. Fig. 2e-f showed that the CCOF-1 and CCOF-2 had a spherical dimension of 250 nm. After modification with poly (ethylene glycol) (PEG), CCOF-1@PEG and CCOF-2@PEG were synthesized while preserving their crystalline structure, imparting exceptional photoluminescent properties, demonstrating remarkable stability, and exhibiting excellent dispersibility. Moreover, CCOF-2@PEG demonstrated efficient generation of reactive oxygen species upon irradiation, as well as high uptake by cancer cells, indicating its potential as a promising PDT agent for cancer treatment (Fig. 2g).

thumbnail Figure 2

(a) Preparation diagram of PgP@Fe-COF NPs. (b) FT-IR spectra of 4 samples. (c) Particle size analysis (blue-PgP@P-COF NPs, red-PgP@Fe-COF NPs). (d) SDT analysis of 2 samples compared with commercial PpIX. Reproduced with permission from Ref. [85], Copyright 2022, John Wiley and Sons. (e) TEM image of CCOF-1@PEG. (f) Particle size analysis of CCOF-2@PEG with TEM upper right. (g) Two weeks of tumor mass measurement. Reproduced with permission from Ref. [90], Copyright 2020, John Wiley and Sons.

Nanosheets COFs

Nanosheet structure is a typical 2D structure with special optical properties, electrical properties and thermal properties [115–118]. Nanosheet COFs are particularly attractive to ROS [119–122]. Gao’s research team reported the development of ultrathin functional porphyrin COF NSs incorporated with carboxyl-rich hyaluronic acid (referred to as HA@COF NSs), which exhibited a distinct lamellar structure (Fig. 3a–c) for enhanced cancer-targeted photodynamic therapy in 2022 [97]. The decreased stacking between layers of HA@COF NSs led to an enhanced ability to generate ROS. In vitro and in vivo tests showed the superior property of HA@COF NSs in PDT, suggesting their potential as a promising option for treating tumors in clinical settings (Fig. 3d). Moreover, Chen and his team developed COF nanosheets decorated with cell membrane-anchoring AuNPs in 2021 [98]. Dox was inserted into holes and pH low insertion peptide (pHILP) was incorporated into the COFs to produce CApHD NSs (Fig. 3g). The results of DLS detections indicated perfect synthesis of each stage (Fig. 3e). When exposed to 635 nm laser, the CApHD NSs produced heat together with ROS directly at the site, disrupting the membranous structure, inducing cell death, and promoting an antitumor immune response (Fig. 3h and i). Simultaneously, Dox was released with laser/pH sensitivity and effectively entered the cell nuclei for chemotherapy (Fig. 3j). In vivo experiments showed that under single laser irradiation, the nanomaterials successfully suppressed the growth of the main tumor and its spread to other parts of the body (Fig. 3f).

thumbnail Figure 3

(a) TEM image of HA@COF NSs (Scale bar: 10 μm). (b) AFM image of HA@COF NSs with its height curve in (c). (d) flow cytometry analysis of the apoptosis of 4T1 cells with various operations. Reproduced with permission from Ref. [97], Copyright 2021, THE SOCIETY. (e) DLS analysis for 2D COF NSs. (f) Adjusted tumor size over a 2-week treatment period. (g) Schematic diagram of the synthesis of the CApHD NSs. (h) Tracing ROS generation with fluorescence detection of DCFH under various irradiation time (0.625 W cm−2). (i) Photothermal detection of two COF NSs (without and with Au) by 635 nm laser. (j) Dox release rate varies under various circumstances. Reproduced with permission from Ref. [98], Copyright 2021, THE SOCIETY.

Nano-rods/tubes COFs

Nanorods and nanotube COFs have unique photoelectric properties, so they are used in cancer therapy [123]. Zhang’s team published a study on a series of nanorods known as COF-909-X (X = Cu, Fe, Ni), which act as triggers for pyroptosis and have the ability to modify the tumor microenvironment to improve tumor immunotherapy in 2022 [106]. The results of TEM images, particle size and zeta potential showed the COF-909-Cu had a distinct rod-like structure (Fig. 4a and b). These COFs showed exceptional superoxide dismutase-like performance, as well as impressive glutathione peroxidase-like capabilities. Tumor size of 4T1 in bearing mice with various conditions (Fig. 4c) showed that the exceptional PTT performance of the three COFs has the potential to enhance the Fenton-like ionization process, leading to increased performance in CDT. Yao’s group developed a carbon nanotube-base π-π conjugated ferriporphyrin COF (COF-CNT) for enhancing nanocatalytic treatment and PDT for tumors in 2021 [107]. The HRTEM image of COF-CNT showed its one-dimensional structure (Fig. 4d). The COF-CNT exhibited the ability to enhance the generation of reactive oxygen species (ROS) and molecular oxygen (O2) within the tumor microenvironment (TME), thereby facilitating self-sustained oxygen delivery during photodynamic therapy (PDT) under near-infrared (NIR) irradiation conditions (Fig. 4f). The experimental results from cell viability of 4T1 cells (Fig. 4e) and tumor volume of the mice (Fig. 4g) with COF-CNT showed that this single treatment effectively leads to complete degeneration of 4T1 breast cancer in mice through immune system regulation.

thumbnail Figure 4

(a) TEM image of COF-909-Cu (Scale bar: 100 nm). (b) Particle size and zeta potential of COF-909-Cu. (c) Tumor size of 4T1 in bearing mice with various conditions. Reproduced with permission from Ref. [106], Copyright 2022, John Wiley and Sons. (d) HRTEM images of COF-CNT (Diffraction rings in lower right). (e) Cell viability of 4T1 with COF-CNT under various treatment (808 nm laser, H2O2). (f) ESR spectra showing 1O2 generation of 4 samples with 808 nm laser. (g) Tumor volume of the mice in 2 weeks with various treatments. Reproduced with permission from Ref. [107], Copyright 2021, Royal Society of Chemistry.

Nanocapsules COFs

Nanocapsule COFs have not only excellent photoelectric properties of COFs, but also unique core-shell structures [124]. Wan’s team carefully designed an enzymatic nanocapsule COF with 3D structure with the ability to efficiently encapsulate horseradish peroxidase (HRP@3D COF) in 2022 (Fig. 5a) [101]. The result of hydrodynamic size showed that there was a strong surface area (800.4 m2 g−1) in this 3D COF (Fig. 5b). Upon acting on the cancer site, the delivered HRP would trigger the oxidation of indole-3-acetic acid and produce ROS that could initiate cell apoptosis and kill the tumor (Fig. 5c). However, the nanocapsules demonstrate a propensity for agglomeration [125]. For this purpose, Chen’s team presented a nano bowl-shape COF with excellent monodispersity and tunable shell-thickness, regardless of the composition, geometry or surface properties in 2021 (Fig. 5e) [75]. The TEM image (Fig. 5f) distinctly showed the bowl-shape structure of the COF treated with SiO2 core.

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(a) Preparation diagram of the 3D COF. (b) Hydrodynamic size of the two 3D COFs. (c) Drug release from HRP@3D COF. (d) Tumor size curves of 2-week in mice under different conditions. Reproduced with permission from Ref. [101], Copyright 2022, THE SOCIETY. (e) Preparation diagram of monodisperse COF-coated SiO2 nanoparticles. (f) TEM image of bowl-shape COF treated with SiO2 core with no treatment upper right (Scale bar: 200 nm). Reproduced with permission from Ref. [75], Copyright 2021, Springer Nature.

In summary, we have compiled a comprehensive inventory of thirty distinct morphologies of COFs materials utilized in tumor therapy, as presented in Table 1. The morphology of COFs plays an important role in cell uptake [76]. Among the thirty COFs materials with different morphologies, COFs with nanospheres account for most of the quantity. The cellular absorption of spherical nanoparticles (NPs) occurs at an accelerated rate compared to other morphologies, due to the increased specific surface area of nano spherical covalent organic frameworks (COFs) facilitates enhanced cell contact, thereby bolstering the rate of cell uptake [74]. Additionally, the two-dimensional structure of Nanosheets COFs confers exceptional capabilities in generating ROS. Nano-rods/tubes COFs have demonstrated their potential to augment the production of ROS and O2 within the TME. Furthermore, nanocapsule COFs possess not only outstanding photoelectric properties but also unique core-shell structures. Subsequent work is expected to do more research on other morphologies of COFs and study the differences in anti-tumor applications of different morphologies of COFs.

RECENT PROGRESS IN COFS FOR CANCER THERAPY

Recently, there has been an obvious increase in the utilization of COFs as vehicles in tumor treatment research. These materials are capable of transporting medicinal compounds to the intended tumor site together with utilizing particularly photothermal and photodynamic properties to eliminate cancerous cells [126,127]. The primary categories of oncotherapy applications incorporating COFs encompass five distinct types: chemotherapy, chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT) and combination therapy [39,128–131]. Here are some typical examples from recent studies.

COFs for chemotherapy

The emergence of diverse nanocarrier systems has brought about new possibilities in the field of effective cancer treatment [132–134]. Nonetheless, most of these nanocarriers continue to grapple with issues of low efficacy and face substantial overcoming various biological obstacles [135–137]. In contrast to typical nanocarriers, covalent organic frameworks (COFs) characterized by their distinctive and appealing attributes demonstrate considerable potential as a viable platform for delivering anticancer drugs [138,139].

Studies have placed greater emphasis on optimizing the structure of COFs for precise targeting and regulation of chemotherapy drug release within the TME [140]. For example, Hassan’s team prepared 9 covalent organic frameworks (COFs 1-9) in 2024 [100]. The schematic structures of COF-1 to COF-9 are shown in Fig. 6a and they were used to pack the drug paclitaxel (PTX+COF), a chemotherapy drug suitable for the treatment of various cancers. The result of porosity analysis showed that COF-3 exhibited permanent porosity (Fig. 6b). FE-SEM analysis of COF-3 revealed its morphological characteristic (Fig. 6c). The studies have shown that the PTX-loaded COF (PTX+COF-3) is more effective at inhibiting metastasis than the drug (PTX) itself. Figure 6d showed that cell viability decreased considerably with increasing concentrations of PTX alone and PTX+COF-3. Gao’s group reported an intelligent development of a COF nanoplatform gated by nucleic acid which was used for specific cancer imaging and could release drug triggered by changing of the microenvironment in 2021 (Fig. 6g) [86]. Doxorubicin (DOX) was stored in COF with surface modification by Cy5 dye-labeled single-stranded DNA (COF was named TpDh-DT). The result shown in Fig. 6e demonstrated that TpDh-DT could release Dox even reached 37.5% under simulated tumor acidic pH after 24 h. As shown in Fig. 6f, TpDh COF NPs had minimal cell damage, and TpDh-DT had a significant inhibition to MCF-10A and MCF-7 cancer cells due to the activated Dox release from TpDh-DT by overexpressed TK1 mRNA as well as acidic microenvironment in tumor cells [141,142].

thumbnail Figure 6

(a) The schematic structures of COF-1 to COF-9. (b) Porosity analysis by low-temperature (77 K) N2 sorption analysis and (c) Morphological analysis by FE-SEM in a scale bar of 200 nm of COF-3. (d) Cell viability decreases considerably with increasing concentrations of PTX alone and in combination with COF-3. Reproduced with permission from Ref. [100], Copyright 2024, American Chemical Society. (e) Dox release of TpDh-DT under various conditions. (f) Cell viability test of MCF-10A and MCF-7 cells treated with three COFs. (g) Schematic drawing of TpDh-DT relating to fabrication, tumor cell imaging, and cancer treatment. Reproduced with permission from Ref. [86], Copyright 2021, American Chemical Society.

COFs have also been used in various stimulus response studies in TME. As shown in Fig. 7a, Wang’s research group prepared a COF consisting of hydrazide and disulfide bonds (HY/SS-CONs), then modified by PEG and loaded with doxorubicin to form DOX-loaded HY/SS-CONs which was pH and redox dual-responsive in 2020 [143]. As shown in Fig. 7b, DOX released from DOX-loaded HY/SS-CONs could achieve approximately 90% in 72 h with GSH under pH 5.0, which indicated that reactive decomposition of HY/SS-CONs induced by both acid and GSH stimuli. Corresponding cell experiment results were shown in Fig. 7c, indicating significant cell inhibition of DOX-loaded HY/SS-CONs. The results of cell experiments were presented in Fig. 7c, illustrating the pronounced inhibitory effect of DOX-supported HY/SS-CONs on tumor cell proliferation. Zhang et al. developed a novel core-shell nanosystem in 2022, consisting of methoxylated COF as the shell and pH-sensitive mitochondria targeting liposome as the core (Fig. 7d) [144], for efficient encapsulation of doxorubicin and camptothecin (CPT@mCOF@DOX-lipid). The release curves of CPT and DOX-lipid in Fig. 7e indicated the fact that CPT and DOX-lipid released much faster at pH 5.0 than 7.4. The CPT@mCOF@DOX-lipid showed significant low-pH-sensitive properties. As shown in Fig. 7f, CLSM pictures of intracellular overall ROS showed that dual loading system of CPT@mCOF@DOX-lipid could increase ROS production compared with individual DOX or CPT.

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(a) Synthesis diagram of DOX-loaded HY/SS-CONs. (b) Dox release from DOX-loaded HY/SS-CONs under various conditions. (c) Fluorescence photographs of HepG2 cells of different treatments for 4 h. Reproduced with permission from Ref. [143], Copyright 2020, Frontiers. (d) Synthesis process of CPT@mCOF@DOX-lipid and its application. (e) Release curves of CPT and DOX-lipid under different pH (5.0 and 7.4). (f) CLSM pictures of intracellular overall ROS by H2DCFDA staining with scale bar of 25 μm). Reproduced with permission from Ref. [144], Copyright 2022, Elsevier.

COFs for chemodynamic therapy (CDT)

Oxidative stress, characterized by the presence of ROS such as singlet oxygen (1O2), hydroxyl radicals (·OH), superoxide anions (O2·−), alkoxyl radicals (RO·), hydrogen peroxide (H2O2), and ozone (O3), has been related to the pathogenesis of diverse disorders including cancer, neurodegenerative diseases, and cardiovascular conditions [145]. The dysregulation of energy metabolism in cancer cells often results in heightened levels of (ROS), particularly hydrogen peroxide (H2O2), which facilitates persistent proliferation and tumorigenesis [146–148]. Terminating the unregulated expansion by perturbing the intracellular equilibrium of ROS represents a viable strategy for treating tumors [149]. An instance is chemodynamic therapy (CDT), which harnesses inorganic catalysts containing Fe, Mn, Cu, and Co to transform the comparatively less harmful H2O2 into the highly toxic ·OH through intracellular Fenton-like reactions, thereby effectively triggering tumor cell mortality [150,151].

The efficacy of CDT as an anti-cancer treatment has been demonstrated in both laboratory and animal model contexts [55]. Current strategies utilizing the CDT frequently encounter limitations due to the intensified and regulated antioxidant defenses within cells [152]. To enhance ·OH-induced CDT cell damage, Zhou’s team prepared a ferro-FC (Fc)-glutathione peroxidase 4 (GPX4) inhibitor-loaded nanomedical drug based on COF, RSL3@COF-Fc (2b) in 2021 (Fig. 8a) [153]. The drug release kinetics of RSL3@COF-Fc (2b) were examined in Fig 8b and c. The results showed that the release rate was much higher under lower pH (pH 5.0), which indicating that differences in pH sensitivity of release rates are ideal for controlling the release rate of drugs under various acidic environments like endosomes and lysosomes, minimizing the unwanted leakage of drugs into normal blood and other body parts [154]. The in vitro antitumor effect caused by ferroptosis of RSL3@COF-Fc (2b) was studied in Fig 8d and e, showing the nanodrug system exhibited targeted toxicity towards the cancer cells.

thumbnail Figure 8

(a) Molecular design and preparation diagram. (b) UV-vis spectra for detecting ·OH production of RSL3@COF-Fc (2b) with different conditions (See Ref. [153] for specific conditions; Respective photos are in the upper right corner). (c) Drug release curves of 1b and 2b at various conditions. (d) HT-1080 and (e) MCF-10A cell viabilities detection under different conditions. (f) In vitro clonogenic research (See Ref. [153] for specific conditions). Reproduced with permission from Ref. [153], Copyright 2021, John Wiley and Sons. (g) Preparation diagram of DOX@COF(Fe) and its application. (h) Flow cytometry of MCF-7/Adr cells under various conditions (See Ref. [155] for specific conditions). (i) Relative tumor growth curves of nude mice under various treatments. Reproduced with permission from Ref. [155], Copyright 2021, THE SOCIETY.

Moreover, to overcome multidrug resistance (MDR) in chemotherapy, Gao et al. reported the preparation of catalytically active Fe-porphyrin based COF loaded with drug DOX (named DOX@COF(Fe)) in 2021 (Fig. 8g) [155]. The result of flow cytometry (Fig. 8h) showed that DOX@COF(Fe) had strong inhibition on tumor cells, reaching enhanced levels of DOX accumulation within the intracellular and intranuclear compartments of MCF-7/Adr tumor cells. The experiment of antitumor models to assess the in vivo impact of COF(Fe) on multidrug-resistant organisms (Fig. 8i) showed that the formation of tumors was slower in DOX, DOX@COF, and COF(Fe) due to their ability to inhibit certain cancer cells. Nevertheless, the DOX@COF(Fe) did not develop any tumor tissue due to the ability of COF(Fe) to enhance the toxicity of DOX and overcome multidrug-resistant effectively.

COFs for photodynamic therapy (PDT)

PDT has been effectively utilized in clinical settings for treating cancer. This non-invasive therapy utilizes an exciting light and photosensitizers (PSs) to generate ROS, which finally result in harm to cancer cells [102,156–159]. PDT offers noninvasive characteristics and precise spatial operation, potentially leading to a reduced frequency of recurrence, decreased total radiation exposure and reduced adverse reactions to a minimum [160–163]. Additionally, COFs possess unique advantages, for example, obvious surface area, controllable porous configuration, and π-π stacking interaction which enable them to achieve high drug loading capacity while minimizing premature drug leakage [164–166]. Furthermore, distinct photoelectric performance makes COFs promising systems for phototherapeutics [96,167–169].

At present, there are many cases of COFs used in PDT treatment of tumors. However, the anoxic status of most solid tumors has a great impact on the efficacy of PDT [170,171], so here are some recent reports on how to solve the problem of anoxia. Currently, there is a growing number of cases involving the utilization of COFs for tumor treatment through PDT. However, the hypoxic condition prevalent in most solid tumors impacts the effectiveness of PDT [170,171]. Therefore, the strategies for addressing the issue of hypoxia have attracted considerable attention in recent research.

Wang’s team designed a 1O2 storage nanomaterial TpDa-COF@Py in 2024 (Fig. 9a) [104]. During laser irradiation by 660 nm, 1O2-enriched COF (TpDa-COF@Py + hv) had been created. UV absorption of DPBF (Fig. 9b) was used to examine the release of 1O2 from EPO, which showed that TpDa-COF + hv was able to produce 1O2 upon pre-irradiation and the absorptivity of DPBF showed minimal reduction after the laser was removed, suggesting a short lifespan for 1O2. As shown in Fig. 9c, the 1O2 QY of TpDa-COF@Py + hv and TpDa-COF + hv were 9.9 % and 32.86 %. Luan’s group synthesized a PyPor-COF connecting the light-sensitive porphyrin units through strong imidazole groups formed in situ in 2022 (Fig. 9d) [172]. Electron paramagnetic resonance experiments (Fig. 9e) showed that the COF could effectively produce 1O2 when exposed to visible light, and anticancer experiment (Fig. 9f) proved that 1O2 could be effectively generated in a biological setting. Wan’s team reported an enzyme nanoprotector with porphyrin-based three-dimensional COF covered with hyaluronic acid (HA) to load catalase (CAT) (CAT@3D COF-HA) in 2022 (Fig. 9g) [173]. Fluctuations of O2 levels under various solutions (Fig. 9h) showed that CAT@3D COF-HA could effectively produce 1O2. The cell viability tests (Fig. 9i) demonstrated that CAT was able to effectively facilitate the breakdown of H2O2 and produce O2 to improve PDT effectiveness even in acidic environments, thanks to the protective properties of 3D COF against extreme pH levels.

thumbnail Figure 9

(a) Synthesis and application of TpDa-COF@Py + hv. (b) UV spectrum of TpDa-COF@Py + hv, TpDaCOF@Py and TpDa-COF + hv at 418 nm. (c) Bar chart of 1O2 production of TpDa-COF + hv and TpDa-COF@Py + hv. Reproduced with permission from Ref. [104], Copyright 2024, Elsevier. (d) Preparation mechanism and process of PyPor-COF. (e) EPR spectra of PyPor-COF and usual singlet oxygen reagents. (f) CLSM images of 4T1 cells with various treatment (Scale bar: 100 μm) (See Ref. [172] for specific conditions). Reproduced with permission from Ref. [172], Copyright 2022, American Chemical Society. (g) Synthesis and application of CAT@3D COF-HA. (h) Fluctuations of O2 levels under various solutions. (i) Cells viabilities of 4T1 treated with various conditions. Reproduced with permission from Ref. [173], Copyright 2022, Elsevier.

In addition to the above hypoxia problem, there are other problems, such as limited water-based dispersibility and inadequate subcellular targeting capability [174,175]. Chen’s team prepared 2 COFs by a gentle solution-phase method with good dispersion named as EB-TFP and DPP-TFP in 2022 (Fig. 10a) [176]. As shown in Fig. 10b and c, EB-TFP and DPP-TFP had significant ROS generation ability and 1O2 production capacity. Cell apoptosis experiment (Fig. 10d) illustrated the viability of Hela cells was notably reduced by DPP-TFP and EB-TFP. Additionally, the molecular engineering of EB-TFP resulted in a higher efficacy compared to DPP-TFP in PDT. Moreover, the anti-tumor effect of PDT is also limited by the quenching of excited states. For this purpose, Zhen’s group reported an unmetalated porphyrin-COF (Ptp) an a protonated and metalated porphyrin-COF (Ptp-Fe) to enhance the PDT efficacy in 2024 [103]. The results of XPS measurements (Fig. 10e) indicated the presence of C, N, Fe, and Cl in Ptp-Fe which indicates the successful incorporation of Fe3+ into Ptp-Fe. Measurement of 1O2 generation (Fig. 10f) and ·OH generation (Fig. 10g) showed that Ptp-Fe had a reduced Type II PDT efficiency compared to Ptp, but it demonstrated a strong Type I PDT effect by producing highly cytotoxic ·OH through its reaction with H2O2. Moreover, under acidic conditions, Ptp-Fe effectively converted H2O2 to ·OH through a photo-enhanced Fenton-like reaction.

thumbnail Figure 10

(a) The synthesis diagram guided by mitochondrial targeting. (b) Production capacity of ROS examined by 525nm white light irradiation. (c) Generation ability of 1O2 examined under 378 nm white light. (d) Confocal photos of HeLa cells with DPP-TFP and EB-TFP under various conditions (Scale bar: 200 μm) (See Ref. [176] for specific conditions). Reproduced with permission from Ref. [176], Copyright 2022, Elsevier. (e) XPS spectra of Ptp and Ptp-Fe. Inset shows the Fe 2p region. (f) 1O2 generation and (g) OH generation of Ptp-Fe with 10 mM PBS at pH 6.5 with or without the addition of H2O2. Reproduced with permission from Ref. [103], Copyright 2024, American Chemical Society.

COFs for photothermal therapy (PTT)

PTT involves using lower wavelength visible light to selectively destroy tumor cells by raising their temperature through photothermal therapy agents (PTAs) [40,177–179]. Competing with other phototherapies, PTT offers excellent benefits including minimal invasiveness, decreased discomfort, and fewer adverse reactions, rendering it an efficient therapy for specific tumors [127,180–182]. Requiring no O2, PTT offers an advantage in the treatment of hypoxic tumors compared to PDT [183–186].

In recent years, some COFs have been used as PTAs that can produce thermal when irradiated and are suitable for use in PTT [187–190]. However, the large structure of COF materials poses challenges in terms of monodispersity, water solubility, and agglomeration [81,190]. To this end, Song’s team prepared a COFs with donor-acceptor (D-A) and coated by polydopamine (PDA) layer and folic acid (FA) molecules (COF-PDA-FA) in 2022 [81]. TEM image of COF-PDA-FA (Fig. 11a) showed that the size was 150 nm after modification with PDA and FA. The experiments on photothermal performance (Fig. 11b and c) demonstrated that the water-soluble COF-PDA-FA exhibited significantly improved photothermal conversion ability compared to COF, which can be attributed not only to the excellent water solubility but also to the inherent photothermal conversion ability of PDA. Furthermore, the adjustment of PDA resulted in an increase in near infrared absorption, thereby enhancing the photothermal conversion efficiency of COF-PDA-FA in aqueous environments [191,192]. Li’s team reported on a water soluble COF (CPF-Cu) with a crimp morphology in 2021 [193]. The TEM (Fig. 11d) showed that the planar dimension of CPF-Cu was determined to be approximately 10 nm, demonstrating effective edge restriction and facilitating the swift penetration of CPF-Cu into cancer cells. In addition to photothermic effects, CPF-Cu was also capable of conducting multicolor imaging (Fig. 11e), as it allowed for the detection of both green and red fluorescence using confocal microscopy. In addition, Xia’s team reported a COFs with electron donor-acceptor (D-A) method that assembled with MPEG2000-DSPE (abbreviated as DPPN COF) in 2021 [184]. The DPPN COF exhibits uniform spherical morphology (Fig. 11f). As shown in Fig. 11g, the DPPN COF exhibited a clear increase in absorbance wavelength, extending into the NIR-II) region (>1000 nm), utilizing a D-A approach. Photothermal experiment of DPPN COF (Fig. 11h) showed that it exhibited the highest photothermal conversion efficiency when exposed to 808 nm laser.

thumbnail Figure 11

(a) TEM image of COF-PDA-FA. (b) Temperature tests of COF-PDA-FA: (b) various concentrations, (c) various current density. Reproduced with permission from Ref. [81], Copyright 2022, Elsevier. (d) The HR-TEM photo of CPF-Cu. (e) Confocal microscope images of SMMC7721 cell treated with CPF-Cu. Reproduced with permission from Ref. [193], Copyright 2021, Elsevier. (f) SEM image of 400 nm spherical COFs. (g) UV spectrum of DPP and DPPN COFs with various sizes in THF. (h) Photothermal temperature curve of water and COFs. Reproduced with permission from Ref. [184], Copyright 2021, American Chemical Society.

For the application of COF in PTT, high photothermal conversion efficiency (PCE) is also extremely important [194,195]. The PCE of different CFS prepared by different methods is different [196]. For instance, Zhang’s team developed a D-A COF incorporating the electron-rich tetrathiafulvalene (TTF) into the layers (TTF-intercalated-COF) in 2023 [94]. Based on the PXRD analysis (Fig. 12a), it is suggested that the monomers PMDA have the potential to undergo polymerization with TAPT in a horizontal orientation, resulting in the formation of 2D crystalline structures. The result of the HOMO-LUMO gap (Fig. 12b) showed this TTF-intercalated COF with D-A structure may lead to an increase in absorption wavelength and improve the effectiveness of photothermal therapy. As a result of the interactions between supramolecular D-A, TTF-intercalated COF had a satisfying PCE up to 38.1% for PTT (Fig. 12c). Xia’s group also prepared a D-A structure COF (named TPAT COF) through Schiff base reaction in 2022 (Fig. 12d) [197]. As shown in Fig. 12e, TPAT COF exhibited a significant photothermal effect and could achieve a considerable PCE of 48.2% (Fig. 12f). Mi’s team reported a 2,2′-bipyridine-based cationic radical COFs (named Py-BPy+•-COF) that has been accomplished by sequential in situ reactions, quaternization, and one-electron reduction in 2019 (Fig. 12g) [99]. Py-BPy+•-COF/PEG produced the highest level of thermal energy, leading to swift temperature rises of up to 75°C and 65°C when exposed to 808 and 1064 nm lasers (Fig. 12h and i). And the PCE of Py-BPy+•-COF was up to 63.8% and 55.2%, respectively.

thumbnail Figure 12

(a) PXRD test for TTF-intercalated COF (Structure diagram inset). (b) HOMO and LUMO surface plots from DFT calculations of TTF-intercalated COF. (c) Photothermal temperature curve of TAPT-PMDA COF and TTF-intercalated-COF. Reproduced with permission from Ref. [94], Copyright 2023, Elsevier. (d) Monomers and the preparation route of TPAT COF. (e) Photothermal temperature curve of TPAT COF under various concentrations. (f) Single heating cooling diagram of TPAT COF. Reproduced with permission from Ref. [197], Copyright 2022, American Chemical Society. (g) Preparation flow chart of Py-BPy+•-COF. Photothermal temperature curves of various PEG-modified COFs under 2 kinds of lasers: (h) 808 nm, (i) 1064 nm. Reproduced with permission from Ref. [99], Copyright 2019, American Chemical Society.

COFs for combination therapy

COFs have found extensive application in nano-drug delivery for chemotherapy, CDT, PDT, and PTT because of their compact pore structure and lipophilicity [159,198–200]. Single treatment methods are not as effective in combating cancer. For example, the self-quenching of photosensitizers in the oxygen-deprived tumor environment can impede the release of ROS, leading to reduced therapeutic efficacy [137,201–203]. Nevertheless, COFs can be linked with diverse materials and changed to become composite nano drug carrying material for various combination therapies, resulting in improved therapeutic outcomes [96,204–206].

The pairwise combinations or three combinations of the four mentioned monotherapies have been realized in recent years. For PDT/PTT combination, Liu’s team prepared a degradable porphyrinic COF (HPCOF) that was triggered by hypoxia for in vivo antitumor treatment in 2024 (Fig. 13a) [207]. The result of ESR spectra (Fig. 13b) showed that HPCOF was capable of generating 1O2 when exposed to 660 nm laser irradiation indicating the photodynamic properties of HPCOF. Moreover, as shown in Fig. 13c, no significant alteration was detected in the maximum temperature for each cycle, suggesting the outstanding photothermal stability of HPCOF.

thumbnail Figure 13

(a) Synthesis and application of HPCOF. (b) ESR tests of HPCOF under various conditions. (c) Temperature curves of HPCOF with 5 heating and cooling cycles. Reproduced with permission from Ref. [207], Copyright 2024, Elsevier. (d) Preparation and application of DOX@COF@HA. (e) Drug release of DOX. (f) Cell survival of 4T1 and MHCC97-L with various conditions. Reproduced with permission from Ref. [91], Copyright 2024, Elsevier. (g) Fluorescence detection pattern of TPE-s COF, TPE-s COF-Au and TPE-s COF-Au@Cisplatin. (h) SEM photos of TPE-s COF-Au@Cisplatin binding to cells (Left: no laser; Right: laser). (i) In vivo fluorescence photos of HepG2-bearing mice with TPE-s COF-Au@Cisplatin, M@TPE-s COFAu@Cisplatin, and PBS under various times. Reproduced with permission from Ref. [95], Copyright 2023, Elsevier.

For the chemotherapy/PDT combination, Chen’s team reported an approximately spherical COF (DOX@COF@HA) with drug doxorubicin (DOX) and embellished by hyaluronic acid (HA) in 2024 (Fig. 13d) [91]. In the presence of normal oxygen levels, the DOX release was 16.9%, but this increased to 60.2% when sodium hydrosulfite was added (Fig. 13e). Results from cell survival tests (Fig. 13f) showed that the combination of PDT with chemotherapy resulted in the lowest survival rates for 4T1 and MHCC97-L. For chemotherapy/PTT combination, Zhou’s group reported a biomimetic multifunctional COF nanozyme (TPE-sCOF-Au@Cisplatin) based on AIEgen-based COF (TPE-s COF), Au NPs and drug Cisplatin with an inactivated form in the HepG2 cell membrane in 2023 [95]. The result of fluorescence spectrum (Fig. 13g) showed that TPE-sCOF-Au exhibited more significant photoluminescence than TPE-sCOF-Au@Cisplatin. Mainly because the presence of Au NPs in TPE-s COF led to obvious increase in aggregation, whereas cisplatin occupied pores of TPE-s COF and inhibited aggregation [208]. SEM photos of cell membrane-specific fusion (Fig. 13h) revealed that upon laser exposure, TPE-s COF-Au@Cisplatin was broken down, leading to the release of TPE-s COF-Au nanozyme and Cisplatin for their photothermal and drug therapeutic activities.

In tumor treatment of COF, there have been some combinations of multi-therapies in recent years. For instance, Wang’s team reported a composite nanosystem (CuS@COFs-BSA-FA/DOX) based on CuS@COFs with bovine serum albumin-folic acid (BSA-FA) as targeting molecule and doxorubicin (DOX) as drug carried for synergistic PTT, chemotherapy and CDT in 2023 (Fig. 14a) [209]. The result of TEM (Fig. 14b) showed that CuS@COFs had a sphere-shaped morphology. The CuS@COFs-BSA-FA/DOX had strong photothermal properties (Fig. 14c) and outstanding performance in Fenton-like catalytic reactions (Fig. 14d), which brought PTT/CDT synergistic therapy. In vitro drug release experiment (Fig. 14e) showed that the acid TEM and NI light induced DOX release from CuS@COFs-BSA-FA/DOX for chemotherapy, then the CDT efficiency of CuS@COFs was enhanced at the same time. Significantly, the focused heat generated by PTT can enhance the effectiveness of CuS@COFs-BSA-FA/DOX in CDT, resulting in a synergistic effect of PTT/chemotherapy/CDT. In addition, Pang et al. reported a COFs-derived O2 and H2O2 self-storing nanosystem (N-CNS-CaO2-HA NCs) that reinforced the combination of CDT, PDT, and PTT for addressing hypoxic tumors in 2024 [93]. As shown in Fig. 14f, the decomposition of CaO2 resulted in the liberation of H2O2. As shown in Fig. 14g, significant oxygen generation was detected in N-CNS-CaO2-HA NCs. The result of Fig. 14h indicated the significant photothermal property of N-CNS-CaO2-HA NCs, and the improvement of their catalytic property could greatly enhance PTT and CDT. Moreover, porous N-CNS-CaO2-HA NCs can transport the photosensitizer (chlorin e6), thereby activating PDT.

thumbnail Figure 14

(a) Synthesis and application of CuS@COFs-BSA-FA/DOX. (b) TEM image of CuS@COFs. (c) Photothermal temperature curve of CuS NPs, CuS@COFs-BSA-FA, TAPB-DMTP-COFs and H2O. (d) Detection of catalytic activity of CuS@COFs with various pH. (e) Drug release of DOX with different conditions. Reproduced with permission from Ref. [209], Copyright 2023, Elsevier. (f) Test of H2O2 production ability of N-CNS-CaO2-HA NCs by UV-vis curve under different conditions. (g) O2 production test of N-CNS-CaO2-HA NCs under different conditions. (h) Photothermal temperature curves of N-CNSs and N-CNS-CaO2-HA NCs. Reproduced with permission from Ref. [93], Copyright 2024, Elsevier.

To sum up, we provide a comprehensive summary of recent progress in the use of COFs for cancer therapy of chemotherapy, CDT, PDT, PTT and combination therapy. From the view of therapeutic effect, combination therapy is more effective than single therapy [159]. But when it comes to single therapy, it is hard to judge. Because each therapy has its mechanism. COFs with chemotherapy are mainly loaded with chemotherapy drugs and used on cancer cells [132]. COFs with CDT, which harness inorganic catalysts containing Fe, Mn, Cu, and Co to transform the comparatively less harmful H2O2 into the highly toxic ·OH through intracellular Fenton-like reactions, thereby effectively triggering tumor cell mortality [150,151]. COFs with PDT utilize an exciting light and PSs to generate ROS, which finally results in harm to cancer cells [102]. COFs with PTT involve using lower wavelength visible light to selectively kill tumor cells by raising their temperature through PTAs [177]. From the previous works mentioned above, COFs with each single therapy have an obvious effect on cancer. However, compared the two phototherapies, PTT offers more benefits than PDT, including minimal invasiveness, decreased discomfort, and fewer adverse reactions, rendering it an efficient therapy for specific tumor. Requiring no O2, PTT offers an advantage in the treatment of hypoxic tumors compared to PDT [127].

CONCLUSIONS AND PERSPECTIVES

In recent years, COFs have been developing as a significant category of biomedical nanomaterials for cancer therapy with good application prospects on account of their high porosity, functionality, and biocompatibility. This review begins with an explicit discussion of COFs with different morphologies in theranostic applications. Subsequently, we provide a comprehensive summary of recent progress in the use of COFs for delivery of chemotherapy, CDT, PDT, PTT and combination therapy. The research showed that COFs are excellent carriers for delivering chemotherapeutic drugs, biomolecules, PSs and/or PTAs. Both in laboratory experiments and in live subjects, the results of using COFs for single or combined therapy were very impressive, demonstrating their ability to effectively inhibit tumor growth. Additionally, we explored how combining therapies with COFs can lead to more effective and synergistic treatment outcomes. However, despite the advantages and encouraging outcomes of COFs in cancer therapies, several challenges and directions warrant further investigation:

(1) As an emerging biomedical material, COFs, especially for the treatment of tumors in vivo, need to pay particular attention to the issues of biocompatibility and biodegradability, which require a large number of in vitro and in vivo studies. In addition, COFs for such applications require rigorous toxicological data (such as long-term systemic toxicity, biosafety, and biodegradation kinetics), as required by the FDA.

(2) Through the combination therapy of COFs summarized by us, we found that combination therapy can indeed improve the defects of single therapy. But from a preparation point of view, it is very difficult to focus two therapies or three or even four therapies on a single COFs nanoplatform.

(3) To ensure the biocompatibility of COFs materials, from the point of view of material size and surface properties, the nanosize of COFs is required to be moderate, the monodispersity is better, and the hydrophilicity is good. This requires accurate preparation methods, and can be developed into large-scale production, with reproducible preparation methods, which requires more research. However, from the perspective of therapies, although the effect of combination therapy is better than that of single therapy, the COFs composition of combination therapy is relatively more complex, which also makes the preparation process of COFs more complicated. So, from this perspective, monotherapy COFs are more likely to achieve reproducible production. This requires finding out the precise preparation temperature, atmosphere, component concentration, time and other factors. It is also necessary to ensure that the performance gap between reproducible -produced COFs and those prepared in the laboratory is not too large.

(4) From the perspective of the antitumor application, except as mentioned chemotherapy, CDT, PDT, PTT, and combination therapy in this review, COFs can be also used for sonodynamic therapy, immunotherapy, starvation-like therapy, radiotherapy etc. Furthermore, COFs can also combine different therapies with medical biomolecular technology, such as nanography technology, gene marker technology, nuclear magnetic resonance technology, etc., which can open u new intervention, detection, and treatment means for cancer treatment. In addition to anti-tumor applications, a large number of literatures has shown that COFs can also be used in sensing, anti-microbials, environmental protection, anti-inflammatory and tissue regeneration.

(5) Finally, regarding the medical application of COFs, our research on the preparation and performance of COFs has been relatively mature, but the evaluation of its biocompatibility has not yet been formed. We need a set of standard evaluation methods for the biocompatibility of COFs to judge whether various COFs materials prepared in the future meet the requirements.

Funding

This work was supported by the National Natural Science Foundation of China (22234005 and 21974070), the Natural Science Foundation of Jiangsu Province (BK20222015), the Young Academic Leaders of the Qing Lan Project of Jiangsu Province (SUJIAOSHIHAN [2022] No.29) and the Industry-University-Research Cooperation Program of Jiangsu Province (BY20230054).

Conflict of interest

The authors declare no conflict of interest.

References

All Tables

Table 1

Summary of recent studies in nanosystems on base of COFs with different morphologies for anticancer applications

In the text

All Figures

thumbnail Figure 1

Schematic illustration of the topics involved in the review.
In the text
thumbnail Figure 2

(a) Preparation diagram of PgP@Fe-COF NPs. (b) FT-IR spectra of 4 samples. (c) Particle size analysis (blue-PgP@P-COF NPs, red-PgP@Fe-COF NPs). (d) SDT analysis of 2 samples compared with commercial PpIX. Reproduced with permission from Ref. [85], Copyright 2022, John Wiley and Sons. (e) TEM image of CCOF-1@PEG. (f) Particle size analysis of CCOF-2@PEG with TEM upper right. (g) Two weeks of tumor mass measurement. Reproduced with permission from Ref. [90], Copyright 2020, John Wiley and Sons.
In the text
thumbnail Figure 3

(a) TEM image of HA@COF NSs (Scale bar: 10 μm). (b) AFM image of HA@COF NSs with its height curve in (c). (d) flow cytometry analysis of the apoptosis of 4T1 cells with various operations. Reproduced with permission from Ref. [97], Copyright 2021, THE SOCIETY. (e) DLS analysis for 2D COF NSs. (f) Adjusted tumor size over a 2-week treatment period. (g) Schematic diagram of the synthesis of the CApHD NSs. (h) Tracing ROS generation with fluorescence detection of DCFH under various irradiation time (0.625 W cm−2). (i) Photothermal detection of two COF NSs (without and with Au) by 635 nm laser. (j) Dox release rate varies under various circumstances. Reproduced with permission from Ref. [98], Copyright 2021, THE SOCIETY.
In the text
thumbnail Figure 4

(a) TEM image of COF-909-Cu (Scale bar: 100 nm). (b) Particle size and zeta potential of COF-909-Cu. (c) Tumor size of 4T1 in bearing mice with various conditions. Reproduced with permission from Ref. [106], Copyright 2022, John Wiley and Sons. (d) HRTEM images of COF-CNT (Diffraction rings in lower right). (e) Cell viability of 4T1 with COF-CNT under various treatment (808 nm laser, H2O2). (f) ESR spectra showing 1O2 generation of 4 samples with 808 nm laser. (g) Tumor volume of the mice in 2 weeks with various treatments. Reproduced with permission from Ref. [107], Copyright 2021, Royal Society of Chemistry.
In the text
thumbnail Figure 5

(a) Preparation diagram of the 3D COF. (b) Hydrodynamic size of the two 3D COFs. (c) Drug release from HRP@3D COF. (d) Tumor size curves of 2-week in mice under different conditions. Reproduced with permission from Ref. [101], Copyright 2022, THE SOCIETY. (e) Preparation diagram of monodisperse COF-coated SiO2 nanoparticles. (f) TEM image of bowl-shape COF treated with SiO2 core with no treatment upper right (Scale bar: 200 nm). Reproduced with permission from Ref. [75], Copyright 2021, Springer Nature.
In the text
thumbnail Figure 6

(a) The schematic structures of COF-1 to COF-9. (b) Porosity analysis by low-temperature (77 K) N2 sorption analysis and (c) Morphological analysis by FE-SEM in a scale bar of 200 nm of COF-3. (d) Cell viability decreases considerably with increasing concentrations of PTX alone and in combination with COF-3. Reproduced with permission from Ref. [100], Copyright 2024, American Chemical Society. (e) Dox release of TpDh-DT under various conditions. (f) Cell viability test of MCF-10A and MCF-7 cells treated with three COFs. (g) Schematic drawing of TpDh-DT relating to fabrication, tumor cell imaging, and cancer treatment. Reproduced with permission from Ref. [86], Copyright 2021, American Chemical Society.
In the text
thumbnail Figure 7

(a) Synthesis diagram of DOX-loaded HY/SS-CONs. (b) Dox release from DOX-loaded HY/SS-CONs under various conditions. (c) Fluorescence photographs of HepG2 cells of different treatments for 4 h. Reproduced with permission from Ref. [143], Copyright 2020, Frontiers. (d) Synthesis process of CPT@mCOF@DOX-lipid and its application. (e) Release curves of CPT and DOX-lipid under different pH (5.0 and 7.4). (f) CLSM pictures of intracellular overall ROS by H2DCFDA staining with scale bar of 25 μm). Reproduced with permission from Ref. [144], Copyright 2022, Elsevier.
In the text
thumbnail Figure 8

(a) Molecular design and preparation diagram. (b) UV-vis spectra for detecting ·OH production of RSL3@COF-Fc (2b) with different conditions (See Ref. [153] for specific conditions; Respective photos are in the upper right corner). (c) Drug release curves of 1b and 2b at various conditions. (d) HT-1080 and (e) MCF-10A cell viabilities detection under different conditions. (f) In vitro clonogenic research (See Ref. [153] for specific conditions). Reproduced with permission from Ref. [153], Copyright 2021, John Wiley and Sons. (g) Preparation diagram of DOX@COF(Fe) and its application. (h) Flow cytometry of MCF-7/Adr cells under various conditions (See Ref. [155] for specific conditions). (i) Relative tumor growth curves of nude mice under various treatments. Reproduced with permission from Ref. [155], Copyright 2021, THE SOCIETY.
In the text
thumbnail Figure 9

(a) Synthesis and application of TpDa-COF@Py + hv. (b) UV spectrum of TpDa-COF@Py + hv, TpDaCOF@Py and TpDa-COF + hv at 418 nm. (c) Bar chart of 1O2 production of TpDa-COF + hv and TpDa-COF@Py + hv. Reproduced with permission from Ref. [104], Copyright 2024, Elsevier. (d) Preparation mechanism and process of PyPor-COF. (e) EPR spectra of PyPor-COF and usual singlet oxygen reagents. (f) CLSM images of 4T1 cells with various treatment (Scale bar: 100 μm) (See Ref. [172] for specific conditions). Reproduced with permission from Ref. [172], Copyright 2022, American Chemical Society. (g) Synthesis and application of CAT@3D COF-HA. (h) Fluctuations of O2 levels under various solutions. (i) Cells viabilities of 4T1 treated with various conditions. Reproduced with permission from Ref. [173], Copyright 2022, Elsevier.
In the text
thumbnail Figure 10

(a) The synthesis diagram guided by mitochondrial targeting. (b) Production capacity of ROS examined by 525nm white light irradiation. (c) Generation ability of 1O2 examined under 378 nm white light. (d) Confocal photos of HeLa cells with DPP-TFP and EB-TFP under various conditions (Scale bar: 200 μm) (See Ref. [176] for specific conditions). Reproduced with permission from Ref. [176], Copyright 2022, Elsevier. (e) XPS spectra of Ptp and Ptp-Fe. Inset shows the Fe 2p region. (f) 1O2 generation and (g) OH generation of Ptp-Fe with 10 mM PBS at pH 6.5 with or without the addition of H2O2. Reproduced with permission from Ref. [103], Copyright 2024, American Chemical Society.
In the text
thumbnail Figure 11

(a) TEM image of COF-PDA-FA. (b) Temperature tests of COF-PDA-FA: (b) various concentrations, (c) various current density. Reproduced with permission from Ref. [81], Copyright 2022, Elsevier. (d) The HR-TEM photo of CPF-Cu. (e) Confocal microscope images of SMMC7721 cell treated with CPF-Cu. Reproduced with permission from Ref. [193], Copyright 2021, Elsevier. (f) SEM image of 400 nm spherical COFs. (g) UV spectrum of DPP and DPPN COFs with various sizes in THF. (h) Photothermal temperature curve of water and COFs. Reproduced with permission from Ref. [184], Copyright 2021, American Chemical Society.
In the text
thumbnail Figure 12

(a) PXRD test for TTF-intercalated COF (Structure diagram inset). (b) HOMO and LUMO surface plots from DFT calculations of TTF-intercalated COF. (c) Photothermal temperature curve of TAPT-PMDA COF and TTF-intercalated-COF. Reproduced with permission from Ref. [94], Copyright 2023, Elsevier. (d) Monomers and the preparation route of TPAT COF. (e) Photothermal temperature curve of TPAT COF under various concentrations. (f) Single heating cooling diagram of TPAT COF. Reproduced with permission from Ref. [197], Copyright 2022, American Chemical Society. (g) Preparation flow chart of Py-BPy+•-COF. Photothermal temperature curves of various PEG-modified COFs under 2 kinds of lasers: (h) 808 nm, (i) 1064 nm. Reproduced with permission from Ref. [99], Copyright 2019, American Chemical Society.
In the text
thumbnail Figure 13

(a) Synthesis and application of HPCOF. (b) ESR tests of HPCOF under various conditions. (c) Temperature curves of HPCOF with 5 heating and cooling cycles. Reproduced with permission from Ref. [207], Copyright 2024, Elsevier. (d) Preparation and application of DOX@COF@HA. (e) Drug release of DOX. (f) Cell survival of 4T1 and MHCC97-L with various conditions. Reproduced with permission from Ref. [91], Copyright 2024, Elsevier. (g) Fluorescence detection pattern of TPE-s COF, TPE-s COF-Au and TPE-s COF-Au@Cisplatin. (h) SEM photos of TPE-s COF-Au@Cisplatin binding to cells (Left: no laser; Right: laser). (i) In vivo fluorescence photos of HepG2-bearing mice with TPE-s COF-Au@Cisplatin, M@TPE-s COFAu@Cisplatin, and PBS under various times. Reproduced with permission from Ref. [95], Copyright 2023, Elsevier.
In the text
thumbnail Figure 14

(a) Synthesis and application of CuS@COFs-BSA-FA/DOX. (b) TEM image of CuS@COFs. (c) Photothermal temperature curve of CuS NPs, CuS@COFs-BSA-FA, TAPB-DMTP-COFs and H2O. (d) Detection of catalytic activity of CuS@COFs with various pH. (e) Drug release of DOX with different conditions. Reproduced with permission from Ref. [209], Copyright 2023, Elsevier. (f) Test of H2O2 production ability of N-CNS-CaO2-HA NCs by UV-vis curve under different conditions. (g) O2 production test of N-CNS-CaO2-HA NCs under different conditions. (h) Photothermal temperature curves of N-CNSs and N-CNS-CaO2-HA NCs. Reproduced with permission from Ref. [93], Copyright 2024, Elsevier.
In the text

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