Near-infrared Photosensitizer Research Articles

Glutathione-responsive Aggregation-induced Emission Photosensitizers for Enhanced Photodynamic Therapy of Lung Cancer.

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.

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.

Self-assembled IR dye/Mitoxantrone loaded Porphysomes Nanosystem for Enhanced Combinatorial Chemo-Photothermal Cancer Therapy

Chemo-photothermal therapy (PTT) is an emerging non-invasive cancer treatment modality. Light-responsive porphysomes (DPP IR Mtx @Lipo NPs) nanosystems ablate breast cancer cells upon oxidative stress and hyperthermia. The unique self-assembled porphysomes were formed spherical shape in the size range of 150 ± 30nm formed by the co-assembly of porphyrins along with IR 775 and chemotherapeutic drug, Mitoxantrone (Mtx), forming a camouflaged nanosystem (DPP IR Mtx @Lipo NPs, porphysomes). The advent of the prepared porphysomes aids in proper tuning of NIR absorbance improving singlet oxygen species generation among other anticancer drugs. The eminent release of DPP and adjuvant chemo-drug, Mitoxantrone from the self-assembled porphysomes is triggered by IR 775, a NIR photosensitizer upon laser irradiation. These multifunctional DPP IR Mtx @Lipo NPs have an efficient photothermal conversion efficiency of 65.8% as well as bioimaging properties. In-vitro studies in 2D and 3D models showed a significant cell death of 4T1 cells via the apoptotic pathway when irradiated with NIR laser, causing minimal damage to nearby healthy cells. DPP IR Mtx @Lipo NPs exhibited commingled PDT/PTT interdependent via NIR laser exposure, leading to mitochondrial disruption. Interestingly, the transient transfection using p53-GFP in cancer cells followed by DPP IR Mtx @Lipo NPs treatment causes rapid cell death. The activation of p53-dependent apoptosis pathways was vividly expressed, evidenced by the upregulation of Bax and increased pattern of Caspase-3 cleavage. This effect was pronounced upon transfection and induction with DPP IR Mtx @Lipo NPs, particularly in comparison to non-transfected malignant breast cancer 4T1 cells.

Three-in-one erlotinib-modified NIR photosensitizer for fluorescence imaging and synergistic chemo-photodynamic therapy

Photodynamic therapy (PDT) presents a promising avenue in cancer treatment. Erlotinib, an FDA-approved anticancer drug targeting epidermal growth factor receptor (EGFR), has shown effectiveness in normalizing tumor vasculature across various tumors, thereby promoting tumor oxygenation and facilitating PDT. In this work, erlotinib was conjugated with a near-infrared (NIR) photosensitizer, benzo[a]phenoselenazinium, yielding three EGFR-targeted PDT agents (NBSe-nC-Er). These newly synthesized photosensitizers demonstrate specificity in binding to EGFR, thereby enhancing their accumulation in cancer cells and tumors, and consequently improving the efficiency of both PDT and chemotherapy. Additionally, the NIR fluorescence emitted by the photosensitizer allows for imaging-guided therapy, offering a non-invasive means of monitoring treatment progress. The distinctive properties of the three-in-one photosensitizer render it an ideal candidate for precise tumor treatment, overcoming the limitations of conventional therapies.

Synergetic Pyroptosis with Apoptosis Improving Phototherapy of Mitochondria-Targeted Cyanines with Superior Photostability.

Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12 was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).

Near-infrared Light-Induced Polymerizations: Mechanisms and Applications.

Photopolymerizations have garnered significant attention in polymer science due to their low polymerization temperature, high production efficiency, environmental friendliness, and spatial controllability. Despite these merits, the poor penetration and severe chemical damage from ultraviolet/visible (UV/Vis) light resources pose significant barriers to their success in conventional photopolymerizations. A recent breakthrough involving the utilization of near-infrared (NIR) laser with long wavelength has been exploited for diverse applications. With the combination of a NIR photosensitizer (PS), NIR-induced photopolymerizations have been successfully developed to alleviate the challenges in conventional methods. The enhancement of penetration depth and safety of NIR-induced photopolymerizations can contribute significantly to improving the efficiency of polymerization for production of intricate structures across various scales. In this concept, the typical types of PSs and polymerization mechanisms (PMs) within the NIR-induced photopolymerization systems have been classified in detail. Additionally, the applications of various polymers achieved by NIR-induced photopolymerizations are summarized. Furthermore, research directions and future challenges of this field are also discussed comprehensively.

γ-glutamyl transpeptidase activatable NIR photosensitizer for visualization and selective killing of liver cancer cells

Photodynamic therapy (PDT) is a treatment model that involves using light sources to excite photosensitizers (PSs), generating reactive oxygen species. This method is considered a potential treatment for tumors. However, the non-selective toxicity of traditional PSs to both tumors and normal tissues hinders the advancement of PDT. This lack of selectivity is a major obstacle in the development of effective PDT. The activatable PS can only function in a specific environment, which enhances the selectivity and safety of PDT. In this paper, we focus on GGT (γ-glutamyltranspeptidase) overexpressed in liver cancer as the biological target. We designed and synthesized the activatable PS BrCy-Glu by modifying the substrate of GGT (l-glutamic acid) onto the brominated hemicyanine PS (BrCy-OH). The intramolecular charge transfer (ICT) effect of BrCy-Glu is inhibited, which leads to low fluorescence quantum yield and singlet oxygen yield. However, in the presence of GGT, it can undergo selective hydrolysis and be converted into BrCy-OH through a series of elimination reactions. This process is accompanied by a significant increase in fluorescence quantum yield and singlet oxygen yield. In vitro studies demonstrate that BrCy-Glu is suitable for precise fluorescence identification of liver cancer and selective eradication of cancer cells under light conditions.

Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

New Type Annihilator of π-Expanded Diketopyrrolopyrrole for Robust Photostable NIR-Excitable Triplet-Triplet Annihilation Upconversion.

Near-infrared light excitable triplet-triplet annihilation upconversion (NIR TTA-UC) materials have attracted interest in a variety of emerging applications such as photoredox catalysis, optogenetics, and stereoscopic 3D printing. Currently, the practical application of NIR TTA-UC materials requires substantial improvement in photostability. Here, we found that the new annihilator of π-expanded diketopyrrolopyrrole (π-DPP) cannot activate oxygen to generate superoxide anion via photoinduced electron transfer, and its electron-deficient characteristics prevent the singlet oxygen-mediated [2 + 2] cycloaddition reaction; thus, π-DPP exhibited superior resistance to photobleaching. In conjunction with the NIR photosensitizer PdTNP, the upconversion efficiency of π-DPP is as high as 8.9%, which is eight times of the previously reported PdPc/Furan-DPP. Importantly, after polystyrene film encapsulation, less than 10% photobleaching was observed for this PdTNP/π-DPP-based NIR TTA-UC material after four hours of intensive NIR light exposure. These findings provide a type of annihilator with extraordinary photostability, facilitating the development of NIR TTA-UC materials for practical photonics.

Enzyme-Activatable Near-Infrared Photosensitizer with High Enrichment in Tumor Cells Based on a Multi-Effect Design.

Enzyme-activatable near-infrared (NIR) fluorescent probes and photosensitizers (PSs) have emerged as promising tools for molecular imaging and photodynamic therapy (PDT). However, in living organisms selective retention or even enrichment of these reagents after enzymatic activation at or near sites of interest remains a challenging task. Herein, we integrate non-covalent and covalent retention approaches to introduce a novel "1-to-3" multi-effect strategy-one enzymatic stimulus leads to three types of effects-for the design of an enzyme-activatable NIR probe or PS. Using this strategy, we have constructed an alkaline phosphatase (ALP)-activatable NIR fluorogenic probe and a NIR PS, which proved to be selectively activated by ALP to switch on NIR fluorescence or photosensitizing ability, respectively. Additionally, these reagents showed significant enrichment (over 2000-fold) in ALP-overexpressed tumor cells compared to the culture medium, accompanied by massive depletion of intracellular thiols, the major antioxidants in cells. The investigation of this ALP-activatable NIR PS in an in vivo PDT model resulted in complete suppression of HeLa tumors and full recovery of all tested mice. Encouragingly, even a single administration of this NIR PS was sufficient to completely suppress tumors in mice, demonstrating the high potential of this strategy in biomedical applications.

Lysosome-targeted Aza-BODIPY photosensitizers for anti-cancer photodynamic therapy

Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 μM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.

Mucus-Penetrating Nanoassembly as Potential Oral Phototherapeutic Formulation against Multi-Drug Resistant Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.

π-extended porphyrin-based near-infrared photosensitizers for mitochondria-targeted photodynamic therapy

Near-infrared (NIR) photosensitizers have great potential to develop various fields of photochemistry, such as photodynamic therapy (PDT) and photocatalysts. Organelle-targeted PDT using NIR light attracts considerable attention to high-efficiency phototherapy. Although drug delivery system (DDS) carriers are often combined with NIR photosensitizers for effective PDT, the systematic correlations between the cargo and DDS carriers are still unclear. In this study, we develop NIR-photosensitizers from a π-extended porphyrin-type sensitizer (rTPA) that allows us to modify the structure and properties with a one-touch operation for the systematic study. Single-step amidations give five rTPA derivatives readily, facilitating comprehensive information about the properties according to their molecular structure and electric charge of the photosensitizer and DDS carriers prepared using a microfluidic device. One of the combinations, rTPA-NH2@MP, demonstrates the highest ability among the derivatives to kill pancreatic cancer cells, which are known to be highly lethal. The present study provides a guideline for inventing effective DDS-based NIR-PDT compounds for future photodrugs.

Endoplasmic reticulum and mitochondrial double-targeted NIR photosensitizer synergistically promote tumor cell death

The excessive production of reactive oxygen species (ROS) can damage the mitochondrial membrane and induce apoptosis, causing endoplasmic reticulum stress and triggering immunogenic cell death. Therefore, the combination of apoptosis and immunogenic death by the dual-targeted ROS generator has great potential to address inefficient cancer treatment. A near-infrared photosensitizer was developed for efficient ROS production and dual-targeted cancer treatment. Due to the modulation of electron structure, the reduced transition energy barrier affords TCy5-I-3F the highest efficiency to produce ROS. TCy5-I-3F has excellent mitochondrial and endoplasmic reticulum targeting ability, causing cell apoptosis and stress of the endoplasmic reticulum for destroying cancer cells. In the dual-targeted mode, high expression of GRP780, activation of heat shock protein (HSP70), the outflow of high mobility group protein B1, efflux of Calreticulin, and massive efflux of adenosine triphosphate are evaluated in the pharmacological experiments. In vivo experiments, the maturation of dendritic cells (DC, CD80+, CD86+), CD8+ T cells and CD3+ T cells also highlights the effectiveness. The tumors of mice treated with TCy5-I-3F and near-infrared (NIR) light are significantly inhibited. The multifunctional targeting design and corresponding mechanisms prove a new insight for exploring efficient photodynamic therapy drugs.

NQO-1 activatable NIR photosensitizer for visualization and selective killing of breast cancer cells

The diagnosis and treatment of breast cancer is of immense importance in improving patient outcomes. The biological marker NAD(P)H:quinone oxidoreductase 1 was utilized to design BrCyS-Q, a near-infrared activatable photosensitizer for breast cancer. BrCyS-Q was successfully employed to diagnose breast cancer cells using fluorescence and photodynamic inhibition. The findings of this research may offer novel insights for the diagnosis and treatment of clinical breast cancer via photodynamic therapy.

HIF‐1α‐inhibited Nanophotosensitizers for Near‐infrared Fluorescence Imaging‐guided Enhanced Photodynamic Therapy

AbstractPhotodynamic therapy (PDT) holds great potential in cancer therapy by virtue of its high precision, non‐invasiveness and low side effect. However, the hypoxic environment of solid tumor significantly restricts the efficacy of PDT. To improve the hypoxic microenvironment, inhibiting the hypoxia‐inducible factor 1α (HIF‐1α) is a rational approach. However, the related small molecule inhibitors suffer from the issue of poor tumor targeting. Herein, we design a nanophotosensitizer AmPPa NP which can inhibit HIF‐1α and conduct PDT with improved efficacy. AmPPa NP is prepared by first encapsulating a hydrophobic NIR photosensitizer mPPa into a carboxyl‐rich amphiphilic copolymer PSMA‐PEG, and then loading a positively charged HIF‐1α inhibitor acriflavine (ACF) on the surface of nanoparticle via electrostatic interaction. Under 635 nm laser irradiation, mPPa within nanoparticles can not only generate 1O2 for PDT but also emit NIR fluorescence signal for tumor imaging. In addition, such design makes ACF can be selectively released under acidic tumor microenvironment. Compared with mPPa NP without ACF loading, AmPPa NP can effectively inhibit HIF‐1α and shows improved PDT efficacy both in vitro and in vivo. This study thus provides a nanotheranostic platform for NIR fluorescence imaging‐guided enhanced PDT.

Near-Infrared Conjugated Polymers Containing Thermally Activated Delayed Fluorescence Units Enable Enhanced Photothermal Therapy.

Photothermal therapy (PTT) using near-infrared (NIR) conjugated polymers as photosensitizers has exhibited enormous potential for tumor treatment. However, most NIR conjugated polymers have poor therapeutic efficacy due to their faint absorbance in the NIR region and low photothermal conversion efficiency (PCE). Herein, a valuable strategy for designing NIR polymeric photosensitizer PEKBs with an enhanced PCE accompanied by strong NIR absorbance is proposed by means of inserting TPA-AQ as a thermally activated delayed fluorescence unit into a polymeric backbone. In these PEKBs, PEKB-244 with the appropriate molar content of the TPA-AQ unit displays the strongest NIR absorbance and the highest PCE of 64.5%. Theoretical calculation results demonstrate that the TPA-AQ unit in the polymeric backbone can modulate the intramolecular charge transfer effects and the excited energy decay routes for generating higher heat. The prepared nanoparticles (PEKB-244 NPs) exhibit remarkable photothermal conversion capacities and great biocompatibility in aqueous solutions. Moreover, PEKB-244 NPs also show outstanding photothermal stability, displaying negligible changes in the absorbance within 808 nm irradiation of 1 h (800 mW cm-2). Both in vitro and in vivo experimental results further indicate that PEKB-244 NPs can substantially kill cancer cells under NIR laser irradiation. We anticipate that this novel molecular design strategy can be employed to develop excellent NIR photosensitizers for cancer photothermal therapy.

Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection

Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.

Near-infrared photosensitizers adaptive to tumor hypoxic microenvironment for synergistic photothermal-photodynamic and immunotherapy

For photodynamic therapy (PDT), traditional type II photosensitizers rely on local molecular oxygen to produce highly cytotoxic singlet oxygen (1O2) to kill tumor cells, which is severely restricted by the hypoxic tumor microenvironment (TME). We herein develop a heavy-metal-free and near-infrared (NIR) photosensitizer BTAC6 and its hydrophilic nanoparticles (BTAC6 NPs) with enhanced tumor-killing effects in both normoxic and hypoxic TME via synergistic photothermal therapy (PTT), PDT (both type I and II) and immunotherapy. BTAC6 possesses donor-acceptor alternating structure (A-DA'D-A) and large-conjugated skeleton, contributing to superb NIR light absorption, narrowed energy gap (ΔEST) and enhanced intersystem crossing (ISC) process for superior PTT and PDT performances. Under the stimulation of 808 nm NIR laser, BTAC6 NPs can adapt to both normoxic and hypoxic TME to effectively ablate tumors. It presents synergistic type II PDT/PTT to generate topical heat and 1O2 in normoxia, and exhibits type I PDT/PTT to produce hyperpyrexia, highly-reactive hydroxyl radical (•OH) and superoxide anion (O2•–) in hypoxia, achieving an over 98 % tumor inhibition rate in mice. Importantly, this synergistic PDT/PTT treatment can activate a durable anti-tumor immune response while destroying the tumors. This work provides a molecular structure design strategy of developing heavy-metal-free NIR photosensitizers to conquer hypoxia.

Near-Infrared BODIPY Photosensitizer for Modulating Mitochondrial Fusion Proteins and Inhibiting Choroidal Neovascularization.

Photosensitizers have emerged as cytotoxic reactive oxygen species (ROS) activators in photodynamic therapy (PDT), which induced cell apoptosis. As the major contributors to ROS and oxidative stress, mitochondria play an important role in cell apoptosis. Although there are many reports about near-infrared 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as photosensitizers (PSs) for PDT, this kind of PS has rarely been used for treating mitochondrial function and choroidal neovascularization application at the same time. Herein, a novel near-infrared PS (BDP2) characterized by good water solubility, long wavelength excitation, and high ROS quantum yield has been made. Under near-infrared light irradiation, BDP2 would generate ROS with high yield, induce a mitochondrial morphology change, and trigger cell apoptosis by changing the fusion protein level. Deep investigation revealed that BDP2 can cause oxidative stress, break the balance between fusion and fission of mitochondrial dynamics protein through decreasing fusion protein MFN2 and OPA1 expression, and finally cause cell apoptosis. Due to these characteristics, the BDP2 PS was used to treat choroidal neovascularization in animal models and can inhibit neovascularization.