Photodynamic Agents Research Articles

The Photodynamic Agent Designed by Involvement of Hydrogen Atom Transferfor Enhancing Photodynamic Therapy.

Although Type-I photodynamic therapy has attracted increasingly growing interest due to its reduced dependence on oxygen, the design of effective Type-I photosensitizers remains a challenge. In this work, we report a design strategy for Type-I photosensitizers by the involvement of hydrogen atom transfer (HAT). As a proof of concept, a HAT-involved Type-I PS, which simultaneously generates superoxide and carbon-centered radicals under light-irradiation, was synthesized. This photosensitizer is comprised of a fluorene-substituted BODIPY unit as an electron acceptor covalently linked with a triphenylamine moiety as an electron donor. Under light-irradiation, photo-induced intramolecular electron transfer occurs to generate the BODIPY anion radical and triphenylamine cation radical. The former transfers electrons to oxygen to generate O2-•, while the latter loses a proton to produce a benzyl carbon-centered radical which is well characterized. The resulting carbon-centered radicals efficiently oxidize NADH by HAT reaction. This photosensitizer demonstrates remarkable photocytotoxicity even under hypoxic conditions, along with outstanding in vivo antitumor efficacy in mouse models bearing HeLa tumors. This work offers a novel strategy for the design of Type-I photosensitizers by involvement of HAT.

The Photodynamic Agent Designed by Involvement of Hydrogen Atom Transfer for Enhancing Photodynamic Therapy

The Photodynamic Agent Designed by Involvement of Hydrogen Atom Transfer for Enhancing Photodynamic Therapy

Hydrogen Sulfide (H2S)activatable Photodynamic Therapy Against Colon Cancer by tunable FRET Effect.

Developing activatable photodynamic agents is becoming a promising mode for realizing selective photodynamic therapy (PDT) in cancer treatment. However, till now only a few H2S-activatable photodynamic agents have been involved in this field. Here, we fabricated H2S-activatable nano-assemblies (P@TPPCY) for the treatment of colon cancer containing high concentration H2S. The H2S-activatable photosensitizer (TPPCY) was synthesized by covalent conjugation between tetraphenylporphyrin (TPP) and heptamethine cyanine (Cy7), and then TPPCY was encapsulated by an amphiphilic polymer DSPE-mPEG to form P@TPPCY nano-assemblies. We demonstrated that the photosensitizing effect of TPP was efficiently quenched by Cy7 with strong absorption in the NIR region via fluorescence resonance energy transfer (FRET) effect. Interestingly, the FRET effect between Cy7 and TPP was attenuated by the decrease of absorption of Cy7 in the NIR region after the Cy7 reacted with H2S, and then the photosensitizing effect of TPP in P@TPPCY was activated. Strikingly, the P@TPPCY showed efficient H2S-activatable photodynamic therapy (PDT) in vitro against HCT116 cells (human colon carcinoma cell line), thus this work provides a new method for realizing accurate treatment of colon cancer in virtue of high H2S concentration microenvironment.

Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT’s efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments.

BODIPY Photosensitizers Functionalized with Mannose for Fluorescence Cell-imaging and Photodynamic Therapy

The synthesis of four water-soluble mannose-tethering BODIPY-based photosensitizers (PSs) with varying substituents (-H, -OMe, -NO2 and -I) in the para-phenyl moiety attached to the meso-position of the BODIPY core, offering tumor-targeting and photodynamic therapeutic (PDT) potentials, is reported. The PDT capability of the synthesized PSs was investigated using the cervical cancer cell line HeLa. Owing to the heavy atom effect, BODIPY I, enhanced the intersystem crossing (ISC) to produce singlet oxygen (1O2) and maintained a high fluorescence quantum yield (ΦF) of 0.71. In contrast, the electron-donating methoxy substituent (BODIPY OMe) caused a notable perturbation in the occupied frontier molecular orbitals, subsequently achieving a higher 1O2 generation capability with a high ΦF of 0.85. Conversely, substitution with the electron-withdrawing nitro group (BODIPY NO2) resulted in a perturbation of unoccupied frontier molecular orbitals and generated a forbidden dark S1 state, negatively affecting both fluorescence and 1O2 generation efficiencies. The cytotoxicity of the synthesized water-soluble BODIPY PSs in the dark and under LED irradiation against the HeLa cell line was also assessed, with BODIPY I, OMe and H showing favorable PDT activity. Collectively, the performance of the mannose-conjugated BODIPY PSs in this study contributed promising results for the development of photodynamic therapeutic agents for cancer treatment.

Upconversion and NIR-II luminescent rare earth nanoparticles combined with machine learning for cancer theranostics.

How to develop contrast agents for cancer theranostics is a meaningful and challenging endeavor, and rare earth nanoparticles (RENPs) may provide a possible solution. In this study, we initially modified RENPs through the application of photodynamic agents (ZnPc) and targeted the bevacizumab antibody for cancer theranostics, which was aimed at improving the therapeutic targeting and efficacy. Subsequently, we amalgamated anthocyanin with the modified RENPs, creating a potential cancer diagnosis platform. When the spectral data were obtained from the composite of cells, the crucial information was extracted through a competitive adaptive reweighted sampling feature algorithm. Then, we employed a machine learning classification model and classified both the individual spectral data and fused spectral data to accurately predict distinctions between breast cancer and normal tissue. The results indicate that the amalgamation of fusion techniques with machine learning algorithms provides highly precise predictions for molecular-level breast cancer detection. Finally, in vitro and in vivo experiments were carried out to validate the near-infrared luminescence and therapeutic effectiveness of the modified nanomedicine. This research not only underscores the targeted effects of nanomedicine but also demonstrates the potent synergy between optical spectral technology and machine learning. This innovative approach offers a comprehensive strategy for the integrated treatment of breast cancer.

Disulfide bond-rich Nano-Silica for High-Efficiency cancer immunotherapy using synergistic endoplasmic reticulum stress cooperated mitochondrial dysfunction

In emerging cancer immunotherapy, the effectiveness of T lymphocytes is primarily hindered by elevated programmed cell death 1 ligand 1 (PD-L1) expression; simultaneously, the shift of tumor-associated macrophages (TAMs) towards tumorigenic M2-type macrophages further abrogates the efficacy of immunotherapy. Accordingly, we rationally designed a glutathione (GSH) responsive disulfide bond-rich nano-silica (DLC-HA) capable of efficient T cells infiltrating and TAMs re-polarization by encapsulating an endoplasmic reticulum (ER)-targeted photodynamic agent p-Ce6 and the glycolysis inhibitor lonidamine (LND), which works together to provoke ER stress and mitochondrial dysfunction. On the one hand, ER stress causes PD-L1 down-expression through ER-associated degradation (ERAD), while also stimulating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. Meanwhile, LND alters mitochondrial dysfunction and activates the AMPK energy pathway, enhancing ER stress and facilitating PD-L1 degradation. On the other hand, ER stress upregulates calreticulin (CRT) expression and mitochondrial dysfunction alleviates hypoxia to downregulate TAMs inhibitory receptor CD47, all of which effectively promotes the phagocytosis and re-polarization of TAMs to anti-tumorigenic M1-type. As expected, this nanoplatform approach, not only activates the immune response of T cells but also facilitates the re-polarization of TAMs in vitro and in vivo assays, offering a novel strategy for efficient cancer immunotherapy using ER stress cooperated mitochondrial dysfunction.

Precise tuning of porphyrin self-assembly and photo-activated antimicrobial activity via metal ion coordination

Bacterial drug resistance has emerged as a significant threat to global human health, prompting the need for alternative antimicrobial strategies. Photodynamic therapy (PDT) has garnered widespread attention as a promising antimicrobial approach that circumvents the issue of bacterial resistance. Porphyrin is a class of photosensitizers with promising potential. In this study, we utilized the strategy of precise tuning of self-assembly of porphyrin through the coordination of metal ions to achieve the efficient and selective photo-activated antimicrobial. Typically, the selected porphyrin (TPPS4) serves as the foundation for an investigation into the role of metal ions (Mn+) as regulatory agents. The coordination of various metal ions (Bi3+, Ca2+, Zn2+, and Mn2+), with TPPS4 results in differentiated molecular stacking, which in turn affects the morphology of the self-assembled structures and their capacity to generate reactive oxygen species (ROS), ultimately leading to varied antimicrobial activities. The study found that the antibacterial capability of the system is positively correlated with its ability to generate reactive oxygen species (TPPS4-Bi ≈ TPPS4-Ca > TPPS4 >TPPS4-Zn >TPPS4-Mn). This work paves the way for the development of novel photodynamic antimicrobial agents that are both highly potent and minimally toxic, offering a significant advancement in the field of antimicrobial therapy.

CuFe2O4/lignin-based carbon composited photothermal and photodynamic agents for synergetic antibacterial therapy

Bacterial infection has become the second leading cause of death in the world. Exploring a new highly antibacterial catalyst to replace traditional antibacterial agent is crucial for the society development of human beings. In this study, CuFe2O4/Lg-based carbon composited catalysts were rationally constructed by facile hydrothermal method. Lignin-derived carbon with enormous oxygen-containing functional group was beneficial to anchor CuFe2O4 nanoparticles. The close contact interface between CuFe2O4 and Lignin-based carbon material was expected to extend the range of optical absorption and promote the separation and transportation of photogenerated carriers. Under NIR (980 nm, 1.5 W/cm2) light irradiation, the as-prepared CuFe2O4/Lg (20 μg/mL) exhibited excellent photo/photothermal synergetic in vitro (against Escherichia coli and Staphylococcus aureus) and in vivo (against Staphylococcus aureus-infected mouse wound model) antibacterial performance. Furthermore, the cell count assay kit 8 (CCK-8 kit) demonstrated the good biocompatibility of this material. On the basis of the experimental results, a possible antibacterial mechanism based on the synergetic photothermal and photodynamic therapies was proposed. This work presented a lignin- derived carbon-based highly efficient antibacterial disinfection agent with desirable biosafety.

A Nanoencapsulated Ir(III)-Phthalocyanine Conjugate as a Promising Photodynamic Therapy Anticancer Agent.

Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.

Towards efficient Ir(III) anticancer photodynamic therapy agents by extending π-conjugation on N^N ligands.

In this work we disclose a new family of biscyclometallated Ir(III) complexes of the general formula [Ir(C^N)2(N^N)]Cl (IrL1-IrL5), where HC^N is 1-phenyl-β-carboline and N^N ligands (L1-L5) are different diimine ligands that differ from each other in the number of aromatic rings fused to the bipyridine scaffold. The photophysical properties of IrL1-IrL5 were thoroughly studied, and theoretical calculations were performed for a deeper comprehension of the respective variations along the series. All complexes exhibited high photostability under blue light irradiation. An increase in the number of aromatic rings led to a reduction in the HOMO-LUMO band gap causing a red-shift in the absorbance bands. Although all the complexes generated singlet oxygen (1O2) in aerated aqueous solutions through a photocatalytic process, IrL5 was by far the most efficient photosensitizer. Consequently, IrL5 was highly active in the photocatalytic oxidation of NADH. The formation of aggregates in DMSO at a high concentration (25 mM) was confirmed using different techniques, but was proved to be negligible in the concentration range of biological experiments. Moreover, ICP-MS studies proved that the cellular uptake of IrL2 and IrL3 is much better relative to that of IrL1, IrL4 and IrL5. The antiproliferative activity of IrL1-IrL5 was investigated in the dark and under blue light irradiation against different cancer cell lines. Complexes IrL1-IrL4 were found to be cytotoxic under dark conditions, while IrL5 turned out to be weakly cytotoxic. Despite the low cellular uptake of IrL5, this derivative exhibited a high increase of cytotoxicity upon blue light irradiation resulting in photocytotoxicity indexes (PI) up to 38. IrL1-IrL4 showed lower photocytotoxicity indexes ranging from 1.3 to 17.0. Haemolytic experiments corroborated the compatibility of our complexes with red blood cells. Confocal microscopy studies proved their accumulation in mitochondria, leading to mitochondrial membrane depolarization, and ruled out their localization in lysosomes. Overall, the mitochondria-targeted activity of IrL5, which inhibits considerably the viability of cancer cells upon blue light irradiation, allows us to outline this PS as a new alternative to traditional chemotherapeutic agents.

Bismuthene nanosheets as a photodynamic and photothermal antibacterial agent under NIR light illumination

Bacterial infections remain a significant public health burden due to the emergence of antibiotic resistance and their non-specific cytotoxic effects, leading to the search for novel antibacterial agents. Two-dimensional (2D) pnictogens, which stand out with their advantegeous properties such as large surface areas, compatibility with biological systems, and permeability across biological membranes, have emerged as potential materials in the fight against bacterial infections. By considering all these advantages, here for the first time, the antibacterial activity of 2D bismuth (Bismuthene, Biene) on Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), Gram-positive Staphylococcus aureus (S. aureus) and Methicillin-Resistant Staphylococcus aureus (MRSA) were examined under NIR light illumination. A growth curve analysis was conducted with a concentration of 256 μg*mL−1 of exfoliated Biene nanosheets to assess the inhibition effect and corresponding antibacterial effect (%) against each bacterial strain. The photodynamic theraphy (PDT) and photothermal therapy (PTT)-mediated antibacterial mechanisms were explored by analyzing the generation of reactive oxygen species (ROS) via Glutathione (GSH) oxidation assay while a photothermal camera monitored temperature dynamic changes during irradiation. The high specific surface area-dependent membrane damage ability of Biene and morphological changes of the bacteria were visualized by field emission scanning electron microscope (FESEM). The exciting growth inhibition activity of Biene nanosheets for all bacterial strains was increased during irradiation, and breathtakingly the inhibition rate reached up to ≥ 99.1 % for P. aeruginosa, S. aureus, and MRSA. Besides, S. aureus and MRSA are more susceptible to Biene than E. coli and P. aeruginosa.

Enzyme-Activatable Near-Infrared Hemicyanines as Modular Scaffolds for in vivo Photodynamic Therapy.

Photodynamic therapy is an anti-cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near-infrared organic photosensitizers are built from large and non-modular structures that cannot be tuned to improve safety and minimize off-target toxicity. This work describes a novel chemical platform to generate enzyme-activatable near-infrared photosensitizers. We optimized the Se-bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin-triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme-activatable Se-bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti-cancer photodynamic therapy agents.

Enzyme‐Activatable Near‐Infrared Hemicyanines as Modular Scaffolds for in vivo Photodynamic Therapy

AbstractPhotodynamic therapy is an anti‐cancer treatment that requires illumination of photosensitizers to induce local cell death. Current near‐infrared organic photosensitizers are built from large and non‐modular structures that cannot be tuned to improve safety and minimize off‐target toxicity. This work describes a novel chemical platform to generate enzyme‐activatable near‐infrared photosensitizers. We optimized the Se‐bridged hemicyanine scaffold to include caging groups and biocompatible moieties, and generated cathepsin‐triggered photosensitizers for effective ablation of human glioblastoma cells. Furthermore, we demonstrated that enzyme‐activatable Se‐bridged hemicyanines are effective photosensitizers for the safe ablation of microtumors in vivo, creating new avenues in the chemical design of targeted anti‐cancer photodynamic therapy agents.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2–•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2–• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

The role of efflux pump inhibitor in enhancing antimicrobial efficiency of Ag NPs and MB as an effective photodynamic therapy agent

Efflux pumps are active transporters, which allow the cell to remove toxic substances from within the cell including antibiotics and photosensitizer complexes. Efflux pump inhibitors (EPIs), chemicals that prevent the passage of molecules through efflux pumps, play a crucial role in antimicrobial effectiveness against pathogen. In this work, we studied the effect of EPI, namely, reserpine, on photodeactivation rate of pathogens when used with Ag NPs and methylene blue (MB). Our results show that using reserpine led to a higher deactivation rate than Ag NPs and MB alone. The mechanism of this observation was investigated with singlet oxygen generation amount. Additionally, different sizes of Ag NPs were tested with reserpine. Molecular docking calculation shows that reserpine had higher affinity toward AcrB than MB. The improvement in bacterial deactivation rate is attributed to blockage of the AcrAB-TolC efflux pump preventing the removal of MB rather than enhanced singlet oxygen production. These results suggest that using reserpine with nanoparticles and photosynthesize is a promising approach in photodynamic therapy.

Biological Performance of Hexadeca-Substituted Metal Phthalocyanine/Reduced Graphene Oxide Nanobioagents.

This study presents a tetra-substituted phthalonitrile derivative, namely, diethyl 2-(3,4-dicyano-2,5-bis(hexyloxy)-6-(4-(trifluoromethoxy)phenoxy)phenyl)malonate (a), cyclotetramerizing in the presence of some metal salts. The resultant hexadeca-substituted metal phthalocyanines [M= Co, Zn, InCl)] (b-d) were used for the modification of reduced graphene oxide for the first time. The effect of the phthalonitrile/metal phthalocyanines on biological features of reduced graphene oxide (rGO) was extensively examined by the investigation of antioxidant, antimicrobial, DNA cleavage, cell viability, and antibiofilm activities of nanobioagents (1-4). The results were compared with those of unmodified rGO (nanobioagent 5), as well. Modification of reduced graphene oxide with the synthesized compounds improved its antioxidant activity. The antioxidant activities of all the tested nanobioagents also enhanced as the concentration increased. The antibacterial activities of all the nanobioagents improved by applying the photodynamic therapeutic (PDT) method. All the phthalonitrile/phthalocyanine-based nanobioagents (especially phthalocyanine-based nanocomposites) exhibited DNA cleavage activities, and complete DNA fragmentation was observed for nanobioagents (1-4) at 200 mg/L. They can be used as potent antimicrobial and antimicrobial photodynamic therapy agents as well as Escherichia coli microbial cell inhibitors. As a result, the prepared nanocomposites can be considered promising candidates for biomedicine.

Alkyl chain engineering of boron dipyrromethenes for efficient photodynamic antibacterial treatment

Photodynamic therapy has been widely employed as an alternative strategy against bacterial infection. Molecular structure has a profound effect on the antibacterial ability of photosensitizers (PSs). Herein, we designed and synthesized a series of boron dipyrromethene (BODIPY)-based photosensitizers with different alkyl chain lengths, and then their antibacterial activities were compared. Among these BODIPYs, the BODIPY with octyl (BDP-8) exhibits the best antibacterial effect, while the antibacterial performance of BODIPY with dodecyl (BDP-12) is the worst. This work provides instructive information for further development of effective photodynamic antimicrobial agents.

A Smart DNA Hydrogel Enables Synergistic Immunotherapy and Photodynamic Therapy of Melanoma.

Immunotherapy faces insufficient immune activation and limited immune effectiveness. Herein, we report a smart DNA hydrogel that enables the release of multivalent functional units at the tumor site to enhance the efficacy of immunotherapy. The smart DNA hydrogel was assembled from two types of ultra-long DNA chains synthesized via rolling circle amplification. One DNA chain contained immune adjuvant CpG oligonucleotides and polyaptamers for loading natural killer cell-derived exosomes; the other chain contained multivalent G-quadruplex for loading photodynamic agents. DNA chains formed DNA hydrogel through base-pairing. HhaI restriction endonuclease sites were designed between functional units. Upon stimuli in the tumor sites, the hydrogel was effectively cleaved by the released HhaI and disassembled into functional units. Natural killer cell-derived exosomes played an anti-tumor role, and the CpG oligonucleotide activated antigen-presenting cells to enhance the immunotherapy. Besides the tumor-killing effect of photodynamic therapy, the generated cellular debris acted as an immune antigen to further enhance the immunotherapeutic effect. In a mouse melanoma orthotopic model, the smart DNA hydrogel as a localized therapeutic agent, achieved a remarkable tumor suppression rate of 91.2 %. The smart DNA hydrogel exhibited enhanced efficacy of synergistic immunotherapy and photodynamic therapy, expanding the application of DNA materials in biomedicine.

Novel near-infrared BODIPY-cyclodextrin complexes for photodynamic therapy

To meet the requirements of diagnosis and treatment, photodynamic therapy (PDT) is a promising cancer treatment with less side-effect. A series of novel BODIPY complexes (BODIPY-CDs) served as PDT agents were first reported to enhance the biocompatibility and water solubility of BODIPY matrix through the click reaction of alkynyl-containing BODIPY and azide-modified cyclodextrin (CD). BODIPY-CDs possessed superior water solubility due to the introduction of CD and their fluorescence emission apparently redshifted (>90 nm) on account of triazole units as the linkers compared to alkynyl-containing BODIPY. Moreover, all the BODIPY-CDs were no cytotoxicity toward NIH 3T3 in different drug concentrations from 12.5 to 200 μg/mL, and had a certain inhibitory effect on tumor HeLa cells. Particularly, BODIPY-β-CD exhibited high reactive oxygen species generation and excellent photodynamic therapy activity against HeLa cells compared to other complexes. The cell viability of BODIPY-β-CD was dramatically reduced up to 20% in the concentration of 100 μg/mL upon 808 nm laser irradiation. This architecture might provide a new opportunity to develop valuable photodynamic therapy agents for tumor cells.