Photosensitizer For Photodynamic Therapy Of Cancer Research Articles

A cell membrane-targeted photosensitizer for cancer photodynamic therapy and dynamic ablation process tracking

Photodynamic therapy (PDT) uses photosensitizer (PS) to generate reactive oxygen species (ROS) under light to trigger cell apoptosis in cancer treatment. Organelle-targeted PS can effectively enhance the efficacy of phototherapy by specifically destroying subcellular organelles. The cell membrane, as an important organelle, is the “protective wall” of cells maintaining the integrity and normal life activities of cells. The damage to cell membranes is fatal to cells. However, utilizing functional PS to achieve cell membrane-targeted PDT, and realize real-time and accurate in situ reporting of cell membrane damage and monitoring of the treatment process, are challenging tasks. In this work, we prepared a photosensitizer (2TPAO) with aggregation-induced emission (AIE) characteristics, good water solubility, strong near-infrared fluorescence, and the capability for specific imaging of cell membranes. Moreover, 2TPAO could effectively produce ROS under visible light irradiation and achieve photodynamic ablation of tumor cells and tumors. Meanwhile, during PDT, the fluorescence changes of 2TPAO indicated the destruction of cell membranes, allowing intuitive determination of the phototherapy results. Therefore, 2TPAO is an effective cell membrane-targeted PS for cancer PDT.

Azide-modified corrole phosphorus complexes for endoplasmic reticulum-targeted fluorescence bioimaging and effective cancer photodynamic therapy

Study on corrole photosensitizers (PSs) for photodynamic therapy (PDT) has made remarkable progress. Targeted delivery of PSs is of great significance for enhancing therapeutic efficiency, decreasing the dosage, and reducing systemic toxicity during PDT. The development of PSs that can be specifically delivered to the subcellular organelle is still an attractive and challenging work. Herein, we synthesize a series of azide-modified corrole phosphorus and gallium complex PSs, in which phosphorus corrole 2-P could not only precisely target the endoplasmic reticulum (ER) with a Pearson correlation coefficient (PCC) up to 0.92 but also possesses the highest singlet oxygen quantum yields (ΦΔ = 0.75). This renders it remarkable PDT activity at a very low dosage (IC50 = 23 nM) towards HepG2 tumor cell line while ablating solid tumors in vivo with excellent biosecurity. Furthermore, 2-P exhibits intense red fluorescence (ΦF = 0.25), outstanding photostability, and a large Stokes shift (190 nm), making it a promising fluorescent probe for ER. This study provides a clinically potential photosensitizer for cancer photodynamic therapy and a promising ER fluorescent probe for bioimaging.

Lysosome-targeting phenalenones as efficient type I/II photosensitizers for anticancer photodynamic therapy

Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.

Zinc Substituted Myoglobin-Albumin Fusion Protein: A Photosensitizer for Cancer Therapy.

Myoglobin combined with human serum albumin (Mb-HSA) can be produced using yeast Pichia pastoris as a host strain, with secretion into the culture medium. This Mb-HSA fusion protein possesses identical O2 binding affinity to that of naked Mb. The Mb unit is reconstituted with a zinc(II) protoporphyrin IX, yielding (zinc substituted Mb)-HSA, ZnMb-HSA. The photophysical property and singlet O2 generation ability of ZnMb-HSA are equivalent to those of ZnMb. In vitro cell experiments revealed that ZnMb-HSA acts as a superior photosensitizer for photodynamic cancer therapy. It is noteworthy that ZnMb-HSA shows long circulation lifetime in vivo.

Structure characterization of an exopolysaccharide from a Shiraia-associated bacterium and its strong eliciting activity on the fungal hypocrellin production

Hypocrellins are fungal perylenequinones (PQs) from Shiraia fruiting bodies and potential photosensitizers for cancer photodynamic therapy. Shiraia fruiting bodies harbor diverse bacterial communities dominated by Pseudomonas. The present study was to characterize the exopolysaccharide (EPS) of P. fulva SB1 which acted as an elicitor to stimulate the PQ accumulation of the host Shiraia. A bacterial EPS named EPS-1 was purified from the culture broth of P. fulva SB1, which consisted of mannose (Man) and glucose (Glc) with an average molecular weight of 9.213 × 104 Da. EPS-1 had (1 → 2)-linked α-mannopyranose (Manp) backbone and side chains of α-D-Manp-(1→ and α-D-Manp-(1 → 6)-β-D-Glcp-(1 → 6)-α-D-Manp(1 → group attached to the O-6 positions of (1 → 2)-α-D-Manp. EPS-1 at 30 mg/L stimulated both intracellular and extracellular hypocrellin A (HA) by about 3-fold of the control group. The EPS-1 treatment up-regulated the expression of key genes for HA biosynthesis. The elicitation of HA biosynthesis by EPS-1 was strongly dependent on the induced reactive oxygen species (ROS) generation. The results may provide new insights on the role of bacterial EPS in bacterium-fungus interactions and effective elicitation strategy for hypocrellin production in mycelial cultures.

Cerium-based nanoparticles for cancer photodynamic therapy

Metal- and metal-oxide-based nanoparticles have been widely exploited in cancer photodynamic therapy (PDT). Among these materials, cerium-based nanoparticles have drawn extensive attention due to their superior biosafety and distinctive physicochemical properties, especially the reversible transition between the valence states of Ce(III) and Ce(IV). In this review, the recent advances in the use of cerium-based nanoparticles as novel photosensitizers for cancer PDT are discussed, and the activation mechanisms for electron transfer to generate singlet oxygen are presented. In addition, the types of cerium-based nanoparticles used for PDT of cancer are summarized. Finally, the challenges and prospects of clinical translations of cerium-based nanoparticles are briefly addressed.

Rational Molecular Design of Efficient Heavy-Atom-Free Photosensitizers for Cancer Photodynamic Therapy.

Photodynamic therapy has emerged as a promising modality for treatment of cancer due to its minimal invasiveness and high selectivity. However, development of advanced photosensitizers (PSs) for clinical translation of photodynamic therapy remains challenging. To overcome the limitations of common photosensitizers containing heavy atoms, we herein developed highly effective heavy-atom-free photosensitizers based on strong donor-π-acceptor-type structures (PTZ-CN and PXZ-CN) for bioimaging and photodynamic ablation of cancer. These PSs exhibited bright fluorescence emission with a large Stokes shift as well as considerable reactive oxygen generation capability under specific conditions. Notably, PTZ-CN could produce reactive oxygen species more efficiently than Ru(bpy)3 2+ (commercial PS) with an approximately 2.2-fold via type I and type II photochemical mechanisms. In addition, their stable nanoparticles were easily formed by self-assembly in an aqueous solution without employing a polymer. More importantly, PTZ-CN/PXZ-CN exhibited bright fluorescence and excellent photodynamic performance with negligible dark cytotoxicity toward HeLa cells. This study demonstrates the promising potential of donor-π-acceptor-type molecule-based PSs in fluorescence image-guided photodynamic therapy.

Development of Novel Tetrapyrrole Structure Photosensitizers for Cancer Photodynamic Therapy.

The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions. Nevertheless, the clinical use of the first-generation PS (sodium porfimer and hematoporphyrins) revealed difficulties, such as long-term skin photosensitivity, insufficient penetration into deep-seated tumors and incorrect localization to it. The second generation is based on different approaches of the synthesis and conjugation of porphyrin PS with biomolecules, which made it possible to approach the targeted PDT of tumors. Despite the fact that the development of the second-generation PS started about 30 years ago, these technologies are still in demand and are in intensive development, especially in the direction of improving the process of optimization split linkers responsive to input. Bioconjugation and encapsulation by targeting molecules are among the main strategies for developing of the PS synthesis. A targeted drug delivery system with the effect of increased permeability and retention by tumor cells is one of the ultimate goals of the synthesis of second-generation PS. This review presents porphyrin PS of various generations, discusses factors affecting cellular biodistribution and uptake, and indicates their role as diagnostic and therapeutic (theranostic) agents. New complexes based on porphyrin PS for photoimmunotherapy are presented, where specific antibodies are used that are chemically bound to PS, absorbing light from the near infrared part of the spectrum. Additionally, a two-photon photodynamic approach using third-generation photosensitizers for the treatment of tumors is discussed, which indicates the prospects for the further development of a promising method antitumor PDT.

The concept and examples of type-III photosensitizers for cancer photodynamic therapy

•A family of oxygen-independent photosensitizers, NBEX, has been developed •The photosensitizers could transmit excited energy to the binding RNA directly •NBEX had excellent killing effect on tumor cells whether in hypoxic condition or not •NBEX showed outstanding tumor-killing performance for different kinds of tumor In conventional photodynamic therapy (PDT), reactive oxygen species are produced to kill cancer cells based on type-I and type-II mechanisms, and the sensitization of photosensitizers is oxygen dependent. However, solid tumors reside in a hypoxic milieu, which hampers the therapeutic efficacy of photosensitive drugs against tumors. Novel photosensitizers NBEX (X = S, Se, Te) were designed to bind to RNA without interference by other species and to transfer excitation-state energy directly to destroy RNA in cancer cells. This process of killing cancer cells is completely independent of oxygen (type-III mechanism). Remarkably, NBEX (X = S, Se, Te) could self-assemble into nanoparticles and accumulate in the tumor area within tens of minutes in vivo. NBESe exhibited an excellent performance for killing solid tumors and inhibited tumor metastasis. Simultaneously, PDT could induce the immune response to tumors. This novel photosensitizer could be a candidate for cancer treatment in clinical practice. In conventional photodynamic therapy (PDT), reactive oxygen species are produced to kill cancer cells based on type-I and type-II mechanisms, and the sensitization of photosensitizers is oxygen dependent. However, solid tumors reside in a hypoxic milieu, which hampers the therapeutic efficacy of photosensitive drugs against tumors. Novel photosensitizers NBEX (X = S, Se, Te) were designed to bind to RNA without interference by other species and to transfer excitation-state energy directly to destroy RNA in cancer cells. This process of killing cancer cells is completely independent of oxygen (type-III mechanism). Remarkably, NBEX (X = S, Se, Te) could self-assemble into nanoparticles and accumulate in the tumor area within tens of minutes in vivo. NBESe exhibited an excellent performance for killing solid tumors and inhibited tumor metastasis. Simultaneously, PDT could induce the immune response to tumors. This novel photosensitizer could be a candidate for cancer treatment in clinical practice.

Dual-step irradiation strategy to sequentially destroy singlet oxygen-responsive polymeric micelles and boost photodynamic cancer therapy

Nanotechnology provides a powerful tool to overcome many disadvantages of small-molecule photosensitizers for photodynamic cancer therapy, such as hydrophobicity, rapid blood clearance, low accumulation in tumor tissue and low cell penetration, etc. The occurrence of quench in photosensitizer-loaded nanoparticle greatly downregulates the ability to generate singlet oxygen with light irradiation. Stimuli-responsive nanocarriers can improve the efficacy of PDT to a certain extent. However, insufficient release of photosensitizer from either endogenous or exogenous stimuli responsive nanocarriers in the short period of light irradiation restricts full usage of the photosensitizer delivered into cancer cells. We here report a dual-step light irradiation strategy to enhance the efficacy of cancer PDT. Ce6 as a photosensitizer is loaded in singlet oxygen-sensitive micelles (Ce6-M) via self-assembly of amphiphilic polymer mPEG2000-TK-C16. After co-incubation of Ce6-M with cancer cells or i.v. injection of Ce6-M, cancer cells or tumor tissues are irradiated with light for a short time to trigger Ce6 release, and 2 h later, re-irradiated for relatively long time. The sufficient release of Ce6 in the period between twice light irradiation significantly improves the generation of singlet oxygen, leading to more efficient cancer therapeutic effects of dual-step irradiation than that of single-step irradiation for the same total irradiation time.

XANTHENE DYES-MEDIATED IN VITRO PHOTODYNAMIC TREATMENT OF CANCER AND NON-CANCER CELL LINES

Rose bengal and erythrosin B are xanthene dyes mainly known and used as antimicrobial agents, but due to their photodynamic activity they are also potential photosensitizers for cancer photodynamic therapy. The aim of this work is to study a photodynamic efficacy of rose bengal and erythrosin B against human skin melanoma and mouse fibroblast cell lines, compare them with each other and find out their photodynamic properties induced by light emitting diodes with total light dose of 5 J/cm2. To fully identify and understand photodynamic properties of both potentially effective photosensitizers, a set of complex in vitro tests such as cell cytotoxic assay, measurement of reactive oxygen species production, mitochondrial membrane potential change assay, mode of cell death determination or comet assay were made. Although both photosensitizers proved to have similar properties such as increasing production of reactive oxygen species with the higher concentration, predominance of necrotic mode of death or genotoxicity, the more effective photosensitizer was rose bengal because its EC50 was over 20 times lower for both cell lines than in case of erythrosin B.

Photosensitizers Based on G-Quadruplex Ligand for Cancer Photodynamic Therapy.

G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric regions and in the promoter and untranslated regions (UTR) of cancer-related genes, such as RAS and MYC. Extensive research has suggested that G4 is a potential molecular target for cancer therapy. Here, we reviewed G4 ligands as photosensitizers for cancer photodynamic therapy (PDT), which is a minimally invasive therapeutic approach. The photosensitizers, such as porphyrins, were found to be highly toxic against cancer cells via the generation of reactive oxidative species (ROS) upon photo-irradiation. Several porphyrin derivatives and analogs, such as phthalocyanines, which can generate ROS upon photo-irradiation, have been reported to act as G4 ligands. Therefore, they have been implicated as promising photosensitizers that can selectively break down cancer-related DNA and RNA forming G4. In this review, we majorly focused on the potential application of G4 ligands as photosensitizers, which would provide a novel strategy for PDT, especially molecularly targeted PDT (mtPDT).

Self-Assembly of Mitochondria-Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia.

The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria-targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self-assemble into spherical micelles directed to mitochondria. Self-assembly of the photosensitizer resulted in a higher photostability by preventing free rotation of the indoline ring of the indocyanine moiety. The mitochondria targeting capability of the photosensitizer allowed it to utilize intramitochondrial oxygen. We found that the mitochondria-targeted photosensitizer localized to mitochondria and induced apoptosis of cancer cells both normoxic and hypoxic conditions through generation of ROS. The micellar self-assemblies of the photosensitizer were further confirmed to selectively localize to tumor tissues in a xenograft tumor mouse model through passive targeting and showed efficient tumor growth inhibition.

An APN-activated NIR photosensitizer for cancer photodynamic therapy and fluorescence imaging

Photodynamic therapy has been developed as a prospective cancer treatment in recent years. Nevertheless, conventional photosensitizers suffer from lacking recognition and specificity to tumors, which causing severe side effects to normal tissues, while the enzyme-activated photosensitizers are capable of solving these conundrums due to high selectivity towards tumors. APN (Aminopeptidase N, APN/CD13), a tumor marker, has become a crucial targeting substance owing to its highly expressed on the cell membrane surface in various tumors, which has become a key point in the research of anti-tumor drug and fluorescence probe. Based on it, herein an APN-activated near-infrared (NIR) photosensitizer (APN-CyI) for tumor imaging and photodynamic therapy has been firstly developed and successfully applied in vitro and in vivo. Studies showed that APN-CyI could be activated by APN in tumor cells, hydrolyzed to fluorescent CyI-OH, which specifically located in mitochondria in cancer cells and exhibited a high singlet oxygen yield under NIR irradiation, and efficiently induced cancer cell apoptosis. Dramatically, the in vivo assays on Balb/c mice showed that APN-CyI could achieve NIR fluorescence imaging (λem = 717 nm) for endogenous APN in tumors and possessed an efficient tumor suppression effect under NIR irradiation.

Perfluorocarbon nanoemulsions containing fluorinated photosensitizer for photodynamic cancer therapy

The composition of the photosensitizer and fluorocarbons with high oxygen capacity allows to increase the effectiveness of photodynamic therapy, which is shown on tumor cells. To achieve the solubility of photosensitizers in fluorocarbons, a number of fluorinated porphyrins were synthesized and their spectral characteristics were obtained. Fluorocarbon emulsions without a photosensitizer are inert for tumor cells of human colon adenocarcinoma. Fluorocarbon nanoemulsion with leader fluorinated porphyrin with fluoroaliphatic substituents accumulates in tumor cells and causes photoinduced necrosis due to peroxidation of membrane lipids. Perfluorocarbon nanoemulsions in combination with a dissolved fluorine phase photosensitizer are promising compositions for the photodynamic therapy of cancer.

A lysosome-localized thionaphthalimide as a potential heavy-atom-free photosensitizer for selective photodynamic therapy

A novel sulfur-substituted naphthalimide (LSNI-S) was synthesized and investigated as a promising lysosome-targeting photosensitizer for photodynamic cancer therapy. The introduction of a dual-functional morpholine group to the 4-position of the naphthalimide backbone combined with the substitution of oxygen atoms by sulfur atoms could facilitate intersystem crossing from the excited singlet state to the reactive triplet state, leading to an excellent singlet oxygen generation efficiency of LSNI-S in organic solvents (ΦΔ ≈ 0.84 in air-saturated acetonitrile). Interestingly, LSNI-S could produce reactive oxygen species via both type-I and type-II mechanisms under physiological conditions. In particular, cell studies demonstrated that LSNI-S selectively localizes in lysosomes of cancer cells and exhibits excellent photodynamic therapy efficacy.

Selective growth of \u03b1-form zinc phthalocyanine nanowire crystals via the flow rate control of physical vapor transport

α-Form zinc phthalocyanine (ZnPc), a kinetically favorable form of ZnPc, is an efficient photosensitizer for photodynamic cancer therapy, especially when it is formed into nanowires (NWs), which have high water dispersibility. To take full advantage of this material, it is necessary to selectively grow kinetically favorable α-form ZnPc NWs over thermodynamically favorable β-form ZnPc NWs. The present study reports the selective growth of kinetically favorable α-form ZnPc NW crystals by a physical vapor transport method with flow rate control of the carrier gas. The flow rate is key for the dominant growth of α-form ZnPc NWs, thus enabling control of the crystal size, which critically affects the stability of ZnPc crystals. The yield of α-form ZnPc NWs was over 98% at a flow rate of 2000 sccm of Ar carrier gas. This approach could be applied for various Pc molecules, including copper phthalocyanine (CuPc). Our findings might contribute to the development of novel strategies for the selective growth of high-quality kinetically favorable crystals with a specific structure and provide great opportunities for their various practical applications.

Synthesis, photophysics, and photochemistry of ball-type phthalocyanines

Phthalocyanines (Pcs) have numerous potential applications, including use as photosensitizers for photodynamic cancer therapy. These applications depend on specific photodynamic properties; therefore, new Pc compounds with unique and well characterized properties are in constant demand. In this study, four novel ball-type Pc compounds were synthesized with 1,2-benzenediol as a substituent, including one non-metal complex (H4Pc2) and three metal-containing complexes (Mg2Pc2, Co2Pc2, and Zn2Pc2). The structures of the synthesized compounds were characterized using common spectroscopic methods. Quantum yields for fluorescence (ΦF), triplet state (ΦT), singlet oxygen (ΦΔ), and photodegradation (Φd) were measured except Co2Pc2 in dimethylsulfoxide. All the three compounds exhibited low fluorescence quantum yield, high triplet quantum yield, and good stability in organic solvent, suggesting acceptable photostability. Complexes with H4Pc2 and Mg2Pc2 demonstrated differences in the Q band in their Uv–Vis spectra. Singlet oxygen quantum yield was 0.35 for Zn2Pc2. Fluorescence lifetimes (τF) for the complexes ranged from 6.67 to 2.95 ns, while triplet state lifetimes (τT) ranged from 50 to 440 μs. This novel group of Pcs possesses properties suitable for photodynamic therapy, particularly ZnPc.

Zinc-substituted hemoglobin with specific drug binding sites and fatty acid resistance ability for enhanced photodynamic therapy

Precisely designed protein-based nanodrugs, as a kind of colloidal drug system, have attracted significant attention in tumor therapy because of their refined drug loading ratio, controlled delivery efficacy and natural biocompatibility. However, most drugs are conjugated to the protein carriers randomly without specific binding sites. Moreover, such sites could easily be replaced by lipophilic molecules in the physiological environment and result in low delivery efficiency. With strong and specific binding locations especially comparatively narrow spatial binding sites and nonflexible structure, hemin (FePPIX)-free hemoglobin or apohemoglobin (apoHb), as a natural metalloporphyrin protein carrier, represents great potential in bioapplication. Therefore, we herein introduce a folate acid (FA) modified, zinc-substituted hemoglobin (ZnPHb-FA) as a naturally occurring protein matrix-based photosensitizer for cancer photodynamic therapy (PDT). Noncovalent inserted ZnPPIX molecules in apoHb possess an extremely stable property and significant recovered photoproperties with superior biocompatibility and phototoxicity, both in vitro and in vivo. This stability was verified by molecular docking analysis and calculation of binding constant, representing a total of five drug binding sites of apoHb for ZnPPIX molecules, four of which are energetically favorable (ΔG value of -11.9 kcal/mol), and one which is energetically acceptable (ΔG value of -9 kcal/mol). Folate acid modification has been shown to efficiently enhance the internalization and retention time of ZnPHb nanodrug. ZnPHb-FA is also an efficient depressor of hemin oxygenase-1 (HO-1), which could, in turn, lower the antioxidant ability of cancer cells by decreasing the production of bilirublin. Results in vitro and in vivo both indicated that the firmly combination of apoHb and ZnPPIX described here represents a novel and efficient protein nanodrug systems for cancer therapy.

Monodispersed CuSe Sensitized Covalent Organic Framework Photosensitizer with an Enhanced Photodynamic and Photothermal Effect for Cancer Therapy.

Attributed to its simplicity, noninvasive features, and excellent therapeutic effect, phototherapy has recently received considerable interest. The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) holds great promise in the treatment of tumors, and in order to achieve satisfactory antitumor efficacy, suitable photosensitizers are a prerequisite. In this paper, highly monodispersed covalent organic framework (COF) nanoparticles were first prepared by a mild solution-phase synthesis method at room temperature. The as-synthesized nonporphyrin containing COF nanoparticle was employed as a novel photosensitizer for PDT, which exhibited an excellent photodynamic effect under 650 or 808 nm laser irradiation. Then, CuSe nanoparticles, an ideal photothermal agent, were successfully conjugated with COF to form a dual functional photosensitizer for phototherapy. The resultant COF-CuSe platform possesses an excellent synergistic photothermal and photodynamic effect. The in vitro and in vivo experiments indicated an enhanced therapeutic effect on killing cancer cells and inhibiting the tumor growth. This work demonstrates the great potential of nonporphyrin containing COF as a photosensitizer for photodynamic cancer therapy and provides a facile and efficient approach to construct COF-based multifunctional theranostic agents for cancer diagnosis and treatment by combining COFs with other functional materials.