Design and Synthesis of Metalloporphyrin Nanoconjugates for Dual Light-Responsive Antimicrobial Photodynamic Therapy

Antimicrobial photodynamic therapy (APDT) utilizes photosensitizers (PSs) that eradicate a broad spectrum of bacteria in the presence of light and molecular oxygen. On the other hand, some light sources such as ultraviolet (UVB and UVC) have poor penetration and high cytotoxicity, leading to undesired PDT of the PSs. Herein, we have synthesized conjugatable mesosubstituted porphyrins and extensively characterized them. Time-dependent density functional theory (TD-DFT) calculations revealed that metalloporphyrin EP (5) is a suitable candidate for further applications. Subsequently, the metalloporphyrin was conjugated with lignin-based zinc oxide nanocomposites (ZnOAL and ZnOKL) to develop hydrophilic nanoconjugates (ZnOAL@EP and ZnOKL@EP). Upon dual light (UV + green light) exposure, nanoconjugates showed enhanced singlet oxygen generation ability and also demonstrated pH responsiveness. These nanoconjugates displayed significantly improved APDT efficiency (4–7 fold increase) to treat bacterial infection under dual light irradiation

Design and Synthesis of Metalloporphyrin Nanoconjugates for Dual Light-Responsive Antimicrobial Photodynamic Therapy

Antimicrobial photodynamic therapy (APDT) utilizes photosensitizers (PSs) that eradicate a broad spectrum of bacteria in the presence of light and molecular oxygen. On the other hand, some light sources such as ultraviolet (UVB and UVC) have poor penetration and high cytotoxicity, leading to undesired PDT of the PSs. Herein, we have synthesized conjugatable mesosubstituted porphyrins and extensively characterized them. Time-dependent density functional theory (TD-DFT) calculations revealed that metalloporphyrin EP (5) is a suitable candidate for further applications. Subsequently, the metalloporphyrin was conjugated with lignin-based zinc oxide nanocomposites (ZnOAL and ZnOKL) to develop hydrophilic nanoconjugates (ZnOAL@EP and ZnOKL@EP). Upon dual light (UV + green light) exposure, nanoconjugates showed enhanced singlet oxygen generation ability and also demonstrated pH responsiveness. These nanoconjugates displayed significantly improved APDT efficiency (4–7 fold increase) to treat bacterial infection under dual light irradiation

Co-Administration of Chemo-Phototherapeutic Loaded Lignin Nanoarchitecture for the Treatment of Skin Cancer Cell Lines and Bacterial Infections

Epidermoid carcinoma is the utmost frequent type of skin cancer worldwide resulting in bacterial infection-induced chronic wounds. The primary available treatment option is surgery and subsequent skin transplantation, which is challenging in terms of associated pain, full cure, skin regeneration, and cost. Combinatorial chemo-phototherapy involving photodynamic therapy and chemotherapy can be a potential treatment for skin cancers and associated chronic wounds. Herein, we devised a multidrug-loaded nanoformulation (RB@CPT-LNPs) by encapsulating Camptothecin (CPT, a chemotherapeutic agent) into biocompatible lignin nanoparticles (LNPs), followed by surface conjugation with Rose Bengal (RB, a photosensitizer). The RB@CPT-LNPs were found to be highly stable (polydispersity, <0.3) in an aqueous solution with size and Zeta potential 170 nm and −14.7 mV, respectively. The RB@CPT-LNPs showed efficient reactive oxygen species generation (ΦΔ, 0.74) in vitro when activated by light. Importantly, RB@CPT-LNPs showed augmented anticancer activity in skin cancer cells (A431) upon 525 nm laser irradiation compared with a single treatment (photodynamic therapy or chemotherapy). Further, the formulation also showed high photodynamic antimicrobial activity against both Gram-positive and Gram-negative bacteria. Therefore, the developed RB@CPT-LNP formulation could offer an effective strategy for the elimination of skin cancer and skin-tumor-induced chronic wounds