Photodynamic Agents Research Articles

Exploring Structure-Activity Relationships in Photodynamic Therapy Anticancer Agents Based on Ir(III)-COUPY Conjugates.

Photodynamic therapy holds great promise as a non-invasive anticancer tool against drug-resistant cancers. However, highly effective, non-toxic, and reliable photosensitizers with operability under hypoxic conditions remain to be developed. Herein, we took the advantageous properties of COUPY fluorophores and cyclometalated Ir(III) complexes to develop novel PDT agents based on Ir(III)-COUPY conjugates with the aim of exploring structure-activity relationships. The structural modifications carried out within the coumarin scaffold had a strong impact on the photophysical properties and cellular uptake of the conjugates. All Ir(III)-COUPY conjugates exhibited high phototoxicity under green light irradiation, which was attributed to the photogeneration of ROS, while remaining non-toxic in the dark. Among them, two hit conjugates showed excellent phototherapeutic indexes in cisplatin-resistant A2780cis cancer cells, both in normoxia and in hypoxia, suggesting that photoactive therapy approaches based on the conjugation of far-red/NIR-emitting COUPY dyes and transition metal complexes could effectively tackle in vitro acquired resistance to cisplatin.

Evaluation of a photodynamic therapy agent using a canine prostate cancer model.

Male dogs can develop spontaneous prostate cancer, which is similar physiologically to human disease. Recently, Tweedle and coworkers have developed an orthotopic canine prostate model allowing implanted tumors and therapeutic agents to be tested in a more translational large animal model. We used the canine model to evaluate prostate-specific membrane antigen (PSMA)-targeted gold nanoparticles as a theranostic approach for fluorescence (FL) imaging and photodynamic therapy (PDT) of early stage prostate cancer. Dogs (four in total) were immunosuppressed with a cyclosporine-based immunosuppressant regimen and their prostate glands were injected with Ace-1-hPSMA cells using transabdominal ultrasound (US) guidance. Intraprostatic tumors grew in 4-5 weeks and were monitored by ultrasound (US). When tumors reached an appropriate size, dogs were injected intravenously (iv) with PSMA-targeted nano agents (AuNPs-Pc158) and underwent surgery 24 h later to expose the prostate tumors for FL imaging and PDT. Ex vivo FL imaging and histopathological studies were performed to confirm PDT efficacy. All dogs had tumor growth in the prostate gland as revealed by US. Twenty-four hours after injection of PSMA-targeted nano agents (AuNPs-Pc158), the tumors were imaged using a Curadel FL imaging device. While normal prostate tissue had minimal fluorescent signal, the prostate tumors had significantly increased FL. PDT wasactivated by irradiating specific fluorescent tumor areas with laser light (672 nm). PDT bleached the FL signal, while fluorescent signals from the other unexposed tumor tissues were unaffected. Histological analysis of tumors and adjacent prostate revealed that PDT damaged the irradiated areas to a depth of 1-2 mms with the presence of necrosis, hemorrhage, secondary inflammation, and occasional focal thrombosis. The nonirradiated areas showed no visible damages by PDT. We have successfully established a PSMA-expressing canine orthotopic prostate tumor model and used the model to evaluate the PSMA-targeted nano agents (AuNPs-Pc158) in the application of FL imaging and PDT. It was demonstrated that the nano agents allowed visualization of the cancer cells and enabled their destruction when they were irradiated with a specific wavelength of light.

Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents.

Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives (1-3) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and 1 O2 emission were obtained only under acidic conditions inducing amine protonation. The pKa values and pH-dependent emissive properties of 1-3 being established, their cellular uptake and activation in the lysosomal vesicles (pH≈4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC50 between 0.16 and 0.06 μM) against HeLa cancer cells.

Homo and heterometallic ruthenium and platinum complexes with multiple targets for therapeutic applications: a review

Abstract We are now well-positioned to comprehend carcinogenesis at a molecular level in greater detail due to significant technological advancements. Additionally, we are now able to rationally design and develop drug molecules with the ability to either selectively enhance or disrupt important biological processes, maximizing their therapeutic potential. This has heralded a new era in drug design. The heterometallic ruthenium–platinum complexes can be used as anticancer, photodynamic therapy, diabetes treatment, and molecular sensors for thiol-containing peptides due to their multifunctional interactions with nuclear DNA, mitochondrial DNA, RNA, and proteins. Compared to cisplatin and its Ru-based monometallic precursors, a significant number of reported ruthenium–platinum complexes exhibit enhanced cytotoxicity and tumor selectivity. Due to the covalent binding of the cis-PtIICl2 moiety to DNA, photoactive Ru(II)–Pt(II) complexes were designed to prelocalize a photodynamic therapy agent at the site of action. The development of ruthenium–platinum-based heterometallic complexes has recently advanced, opening up new avenues for the development of drugs that are more efficient. Metal complexes’ potential as important cancer therapeutic agents will be the primary focus of this review. The development of ruthenium and platinum-based mono and mixed-metal complexes with therapeutic and biomedical applications are discussed in detail in this article.

Single Component Organic Photosensitizer with NIR-I Emission Realizing Type-I Photodynamic and GSH-Depletion Caused Ferroptosis Synergistic Theranostics.

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Tuning the Photophysical Properties of Ru(II) Photosensitizers for PDT by Protonation and Metallation: A DFT Study.

Due to their activity, photosensitizers with the Ru(II)-polypyridyl complex structure represent an intriguing class of photodynamic therapy agents used to treat neoplasms. However, their solubility is poor, intensifying experimental research into improving this property. One recently proposed solution is to attach a polyamine macrocycle ring. In this paper, the density functional theory (DFT) and time-dependent DFT (TD-DFT) studies on such derivative were performed to assess the impact of the protonation-capable macrocycle and its ability to chelate transition state metals, as illustrated by the Cu(II) ion, on the expected photophysical activity. These properties were determined by examining ultraviolet-visible (UV-vis) spectra, intersystem conversion, and type I and II photoreactions of all species possibly present in a tumor cell. For comparison purposes the structure devoid of the macrocycle was also examined. The results show that the subsequent protonation of amine groups improves the reactivity, with [H2L]4+/[H3L]5+ being borderline, whereas complexation appears to weaken the desired photoactivity.

Up-regulation of ABCG2 by MYBL2 deletion drives Chlorin e6-mediated photodynamic therapy resistance in colorectal cancer

ObjectivePhotodynamic therapy (PDT) may be an effective therapeutic strategy for colorectal cancer at an early stage. However, malignant cells’ resistance to photodynamic agents can lead to treatment failure. MYBL2 (B-Myb) is an oncogene in colorectal carcinogenesis and development, for which little research has focused on its effect on drug resistance. Materials and MethodsIn the present work, a colorectal cancer cell line with a stable knockdown of MYBL2 (ShB-Myb) was constructed first. Chlorin e6 (Ce6) was utilized to induced PDT. The anti-cancer efficacy was measured by CCK-8, PI staining, and Western blots. The drug uptake of Ce6 was assayed by flow cytometry and confocal microscopy. The ROS generation was detected by the CellROX probe. DDSB and DNA damage were assayed through comet experiment and Western blots. The over-expression of MYBL2 was conducted by MYBL2 plasmid. ResultsThe findings indicated that the viability of ShB-Myb treated with Ce6-PDT was not decreased compared to control SW480 cells (ShNC), which were resistant to PDT. Further investigation revealed reduced photosensitizer enrichment and mitigated oxidative DNA damage in colorectal cancer cells with depressed MYBL2. It turned out that SW480 cells knocking down MYBL2 showed phosphorylation of NF-κB and led to up-regulation of ABCG2 expression thereupon. When MYBL2 was replenished back in MYBL2-deficient colorectal cancer cells, phosphorylation of NF-κB was blocked and ABCG2 expression up-regulation was suppressed. Additionally, replenishment of MYBL2 also increased the enrichment of Ce6 and the efficacy of PDT. ConclusionIn summary, MYBL2 absence in colorectal cancer contributes to drug resistance by activating NF-κB to up-regulate ABCG2 and thereby leading to photosensitizer Ce6 efflux. This study provides a novel theoretical basis and strategy for how to effectively improve the anti-tumor efficacy of PDT.

Abstract 2381: Gold nanorods functionalized with an alpha5beta1 ligand: a simple and robust nanosystem for early bladder cancer detection

Abstract Early detection and removal of bladder cancer (BC) is crucial to prevent tumor recurrence and progression. Various imaging modalities have been used to diagnose BC, including computed tomography urography, intravenous urography, ultrasound echography, multiparametric magnetic resonance imaging, cystoscopy, and cystoscopy in conjunction with intravesical instillation of hexaminolaevulinic acid, a photodynamic diagnostic agent. However, all these imaging techniques show a very poor detection rate of small (<5mm) and flattened cancer lesions. Because of this limitation, patients with BC frequently relapse after initial diagnosis and need frequent follow-ups and treatments, resulting in a poor quality of life. For the same reason, BC has the highest cost/patient among all cancers. We have recently developed a new methodology to detect bladder cancer lesions based on bladder instillation with GNRs@Chit-Iso4, a nanosystem consisting of gold nanorods (GNRs) decorated with chitosan and functionalized with the head-to-tail cyclized [CphgisoDGRG] peptide (Iso4, a selective ligand of alpha5beta1-integrin expressed by BC cells), followed by low-frequency ultrasound-assisted shaking of nanoparticles necessary to prevent their sedimentation, and photoacoustic imaging of targeted tumor lesions. In murine models, this procedure can detect orthotopic BC lesions <0.5 mm, undetectable by standard imaging modalities (Alchera et al., Photoacoustic, 2022). In the attempt to develop a simpler and more effective imaging modality of BC, we have produced and preclinically evaluated new GNRs decorated with lipoic acid-polyethylene glycol (PEG -5KDa) and functionalized with Iso4. The resulting product, obtained by a simple 2-step procedure and called GNRs@PEG5K-Iso4, efficiently recognized alpha5beta1- and alpha5beta1-expressing cells, was stable in 90% urine, and was resistant to freezing- or salt-induced aggregation.GNRs@PEG5K-Iso4 did not undergo sedimentation after instillation into the bladder, thereby avoiding the need of the complex ultrasound-assisted shaking of nanoparticles and could efficiently detect BC lesions smaller than <0.5 mm in murine models. These results suggest that GNRs@PEG5K-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and early diagnosis of small BC lesions. Citation Format: Massimo Alfano, Elisa Alchera, Angelina Sacchi, Alessandro Gori, Irene Locatelli, Anna Maria Gasparri, Barbara Colombo, Giulia Anderluzzi, Paolo Armanetti, Luca Minichetti, Andrea Salonia, Angelo Corti, Flavio Curnis. Gold nanorods functionalized with an alpha5beta1 ligand: a simple and robust nanosystem for early bladder cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2381.

Polypyridyl CoII -Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents.

Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.

Preparation and characterization of curcumin/chitosan conjugate as an efficient photodynamic antibacterial agent

Curcumin (Cur) is a natural pigment with excellent biological activity. The poor stability and insolubility of Cur in water severely limit its application. Therefore, to overcome these dilemmas which are big hindrances in their application, a novel derivative (COCS-Cur) was prepared by the esterification reaction of carboxylated chitosan (COCS) and Cur. The structure and properties of conjugate were determined through a series of characterizations. The derivatives had excellent solubility as well as stability. In addition, antioxidant and photodynamic antibacterial experiments proved that COCS-Cur had the excellent free radical scavenging ability and photodynamic antibacterial activity. The derivatives presented a better antibacterial effect on Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli). Noteworthy, the COCS-Cur derivatives showed no obvious toxicity which makes them a stronger contender and potential antimicrobial agent or functional nutrient for application in the food industry.

Recent Developments in Nanoparticle-Based Photo-Immunotherapy for Cancer Treatment.

Phototherapy is an emerging approach for cancer treatment that is effective at controlling the growth of primary tumors. In the presence of light irradiation, photothermal and photodynamic agents that are delivered to tumor sites can induce local hyperthermia and the production of reactive oxygen species, respectively, that directly eradicate cancer cells. Nanoparticles, characterized by their small size and tunable physiochemical properties, have been widely utilized as carriers for phototherapeutic agents to improve their biocompatibility and tumor-targeted delivery. Nanocarriers can also be used to implement various codelivery strategies for further enhancing phototherapeutic efficiency. More recently, there has been considerable interest in augmenting the immunological effects of nanoparticle-based phototherapies, which can yield durable and systemic antitumor responses. This review provides an overview of recent developments in using nanoparticle technology to achieve photo-immunotherapy.

Photo-controllable burst generation of peroxynitrite based on synergistic interactions of polymeric nitric oxide donors and IR780 for enhancing broad-spectrum antibacterial therapy.

The newly attractive peroxynitrite (ONOO-) therapy can prominently enhance antibacterial therapeutic efficacy. However, it is a great challenge but urgently needed to generate ONOO- with adjustable release rate and dosage in order to satisfy personalized treatments for different disease types and severities. Herein, PSNO@IR780 nanoparticles are fabricated via co-assembly of an amphiphilic PEG-b-PAASNO block copolymer grafted with abundant nitric oxide (NO) donor units and IR780 as a photothermal and photodynamic agent. Photo-controllable burst generation of ONOO- from PSNO@IR780 nanoparticles could be realized based on synergistic reactions of rapid NO release induced by increased local temperature and efficiently produced superoxide anion radical (O2•-) from IR780. The maximum ONOO- release dosage is up to 6.73 ± 0.07 µM and release rate is up to 98.1 ± 1.38 nM/s. Furthermore, the ONOO- release behavior can be precisely manipulated by varying sample concentrations, irradiated durations, output power densities, and laser switches, respectively. Ultra-efficiently generated ONOO- from biocompatible PSNO@IR780 nanoparticles significantly elevated broad spectrum antibacterial efficiency through damaging bacterial membranes. Thus, PSNO@IR780 nanoparticles may present a new insight into preparation of burst and controllable generating ONOO- materials, and provide new opportunities for antibacterial therapy. STATEMENT OF SIGNIFICANCE: 1. Polymeric NO donor (PEG-b-PAASNO) grafted with abundant NO donor units was synthesized. 2. PSNO@IR780 nanoparticles were prepared by co-assembly of IR780 and amphiphilic PEG-b-PAASNOpolymer. 3. The maximum ONOO- release dosage from PSNO@IR780 nanoparticles was 6.73 ± 0.08µM. 4. The fastest ONOO- release rate from PSNO@IR780 nanoparticles was 98.1 ± 1.4nM/s. 5. Ultra-efficiently generated ONOO- significantly elevated antibacterial efficiency via damaging bac-terial membranes.

Light excitation of gold Nanorod-Based hybrid nanoplatforms for simultaneous bimodal phototherapy

In this work, we developed a hybrid nanosystem able to simultaneously combine its potential as a photodynamic (PDT) and plasmonic photothermal (PPTT) therapeutic agent to kill malignant cells. To do that, AuNRs were functionalized by means of the layer-by-layer (LbL) assembly technique using alternating layers of anionic poly(styrene sulfonate) (PSS) and cationic poly-L-lysine (PLL) as polyelectrolytes (PEs), and an outer final layer of hyaluronic acid (HA) to provide the hybrid particles with both sufficient colloidal stability and targeting ability to tumoral cells overexpressing CD44 receptors. To provide the nanoplatform with PDT capabilities, the near-infrared (NIR) sensitive photosensitizer (PS) indocyanine green (ICG) was previously grafted to the PLL PE and assembled on the particle surface coating; in this manner, PSS/PLL-ICG/HA-coated AuNRs hybrid particles were obtained. Then, the conditions for optimized reactive oxygen species (ROS) production under NIR light excitation were elucidated, reaching ca. 80% after 5 min irradiation at 2.0 W/cm2 compared to positive control (H2O2). Since ICG can also absorb near infrared (NIR) light and transforms it by internal conversion into heat under suitable irradiation conditions, which adds to the photothermal plasmonic effect provided by the metallic NP, the heating profiles provided by the present hybrid nanoparticles (NPs) were measured, being observed temperature increments ranging from 9 to 22 °C. The potential contribution of its different components to both PDT and PPTT were deeply analyzed in vitro for intended cancer therapeutics at several power intensities but also at different temperatures with the aim of elucidating the role played by both phototherapies on cell cytotoxicity, the optimal illumination conditions for effective bimodal phototherapy as well as the elucidation of the main cell death mechanism involved. Under optimized conditions and after the administration of 2.5 ·1010 NPs/mL, cell cytotoxicites of up to ca. 70% were determined by combination of PDT + PPTT therapeutic effect.

Inside Back Cover: Bandgap‐Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy (Angew. Chem. Int. Ed. 12/2023)

Preparation of two-dimensional nanosheets with suitable band gap has been a challenge for their photodynamic applications. In their Research Article (DOI: 10.1002/anie.202215795), Min Ge, Jianlin Shi et al. report a cutting-edge regulatory approach to create H-terminated germanene with a bio-medically favorable direct band gap by a simple surface chemical modulation for bio-application in cancer photodynamic therapy.

Innenrücktitelbild: Bandgap‐Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy (Angew. Chem. 12/2023)

The preparation of 2D nanosheets with suitable bandgaps for photodynamic applications has been a challenge. In their Research Article (e202215795), Han Lin, Jianlin Shi, and co-workers report a cutting-edge regulatory approach to create H-terminated germanene with a biomedically favorable direct bandgap by simple surface chemical modulation for application in cancer photodynamic therapy.

Bandgap‐Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy

AbstractTwo‐dimensional (2D) monoelemental materials (Xenes) show considerable potential in bioapplications owing to their unique 2D physicochemical features and the favored biosafety resulting from their monoelemental composition. However, the narrow band gaps of Xenes prevent their broad applications in biosensors, bioimaging and phototherapeutics. In this study, it is demonstrated that 2D germanene terminated with −H via surface chemical engineering, shows a much broadened direct band gap of 1.65 eV, which enables the material to be used as a novel inorganic photosensitizer for the photodynamic therapy of singlet oxygen. Through theoretical analysis and in vitro studies, H‐germanene nanosheets demonstrate a substantially enlarged band gap and favorable biodegradability, demonstrating a substantial cancer treatment capacity. This study demonstrates the feasibility of constructing novel therapeutic photodynamic agents by surface covalent engineering for catalytic tumor therapy.

Bandgap-Engineered Germanene Nanosheets as an Efficient Photodynamic Agent for Cancer Therapy.

Two-dimensional (2D) monoelemental materials (Xenes) show considerable potential in bioapplications owing to their unique 2D physicochemical features and the favored biosafety resulting from their monoelemental composition. However, the narrow band gaps of Xenes prevent their broad applications in biosensors, bioimaging and phototherapeutics. In this study, it is demonstrated that 2D germanene terminated with -H via surface chemical engineering, shows a much broadened direct band gap of 1.65 eV, which enables the material to be used as a novel inorganic photosensitizer for the photodynamic therapy of singlet oxygen. Through theoretical analysis and in vitro studies, H-germanene nanosheets demonstrate a substantially enlarged band gap and favorable biodegradability, demonstrating a substantial cancer treatment capacity. This study demonstrates the feasibility of constructing novel therapeutic photodynamic agents by surface covalent engineering for catalytic tumor therapy.

Supramolecular Photosensitizer Enables Oxygen-Independent Generation of Hydroxyl Radicals for Photodynamic Therapy.

The highly oxygen-dependent nature of photodynamic therapy (PDT) limits its therapeutic efficacy against hypoxic solid tumors in clinics, which is an urgent problem to be solved. Herein, we develop an oxygen-independent supramolecular photodynamic agent that produces hydroxyl radical (•OH) by oxidizing water in the presence of intracellularly abundant pyruvic acid under oxygen-free conditions. A fluorene-substituted BODIPY was designed as the electron donor and coassembled with perylene diimide as the electron acceptor to form the quadruple hydrogen-bonded supramolecular photodynamic agent. Detailed mechanism studies reveal that intermolecular electron transfer and charge separation upon light irradiation result in an efficient generation of radical ion pairs. Under oxygen-free conditions, the cationic radicals directly oxidize water to generate highly cytotoxic •OH, and the anionic radicals transfer electrons to pyruvic acid, realizing the catalytic cycle. Thus, this photodynamic agent exhibited superb photocytotoxicity even under severe hypoxic environments and excellent in vivo antitumor efficacy on HeLa-bearing mouse models. This work provides a strategy for constructing oxygen-independent photodynamic agents, which opens up an avenue for effective PDT against hypoxic tumors.

Inhibition of Self-Assembling Peptide Fibrils Formation Using Thioflavin T as a Photosensitizer

Misfolded proteins produce fibrillar aggregates, which contain β-sheet higher order structures. The oligomers, protofibrils, and fibrils generated during protein aggregation process are cytotoxic and can cause various neurodegenerative diseases. Recently the photo-active materials, the photosensitizers, have attracted increased attention in the study and treatment of amyloid-related diseases. Here, we studied the photodynamic effect of the amyloid-specific fluorescence dye Thioflavin T on the formation of self-assembled peptide hydrogel. It was demonstrated that the gelation process under irradiation inhibits significantly, at that the structural and mechanical properties of mature fibrils change notably suggesting that ThT could be regarded as a theranostic probe. The developed peptide model allows for quantification of the photodynamic agent’s efficiency in preventing aggregation, thus paving the way for a high-throughput test system for screening of light-responsive theranostic agents.

Identification of a luminescent platinum(II) complex with BODIPY derivative as novel photodynamic therapy agent for triple negative breast cancer cells

Triple-negative breast cancer (TNBC) is one of the most malignant breast tumors for its poor prognosis and high tumor recurrence. It is urgent to develop new strategy or effective agents to overcome resistance and improve therapeutic effectiveness. Boron-dipyrromethene (BODIPY) based photosensitizers possess exciting photophysical features suitable for theranostic applications, namely, photodynamic therapy (PDT). We have designed a luminescent monofunctional platinum(II) complex with BODIPY derivative, namely I2BC-Pt, as novel high PDT agent against triple negative breast cancer (TNBC). The di-iodinated BODIPY complex I2BC-Pt showed excellent PDT effect against TNBC cells in green light (520 nm) giving IC50 values of 0.11–0.13 μM in MDA-MB-231 and MDA-MB-468 cells. I2BC-Pt predominately aggregated in the mitochondria of MDA-MB-231 cells and emitted green fluorescence. Besides, the anticancer mechanism studies demonstrated that I2BC-Pt could help DNA repair through attenuating RAD51, FoxM1 and BRCA1/2, and induce p53-mediated apoptosis of TNBC cells. Taken together, I2BC-Pt could be potentially developed as a BODIPY-based photosensitizers for TNBC therapy.