Development of Gold-Based Phototheranostic Nanoagents through a Bioinspired Route and Their Applications in Photodynamic Therapy

Green synthesis of nanoparticles using phytoconstituents has been widely accepted. However, further applications for delivery, diagnosis, and therapy are not yet fully established. Thus, bioinspired nanomedicinal diagnostic agents have been developed with antioxidant, diagnostic, as well as therapeutic properties. The sustainable biological synthesis of fluorescent gold nanoparticles using <i>Syzygium cumini</i> fruit extract presents a simplified process for the production of surface-functionalized nanoparticles with good antioxidant potential. The gold-based phototheranostic nanoagents (PTNAs) were engineered by conjugating nanoparticles either with a photosensitizer (rose bengal or pyridyl porphyrin) or with an imaging agent (rhodamine B). The assembled PTNAs were revealed to possess good fluorescent properties and to generate singlet oxygen, and showed antimicrobial properties when irradiated with low-cost green LED light. All of the processes and properties (synthesis, antioxidant potential, percent conjugation, fluorescence, singlet oxygen generation, and antimicrobial photodynamic therapy) of PTNAs synthesized using <i>S. cumini</i> were characterized and compared with those synthesized using chitosan. The antimicrobial effect of photodynamic therapy using developed PTNAs was characterized by confocal laser scanning microscopy (CLSM). The development of bioinspired PTNAs described herein will find applications of photodynamic therapy for the treatment of cancer and microbial infection

Design, Sustainable Synthesis, and Programmed Reactions of Templated <i>N</i>‑Heteroaryl-Fused Vinyl Sultams

A de novo design and synthesis of <i>N</i>-heteroaryl-fused vinyl sultams as templates for programming chemical reactions on vinyl sultam periphery or (hetero)­aryl ring is described. The key features include rational designing and sustainable synthesis of the template, customized reactions of vinyl sultams at CC bond or involving N–S bond cleavage, and reactions on the periphery of the heteroaryl ring for late-stage diversification. The simple, easy access to the template coupled with opportunities for the synthesis of diversely functionalized heterocyles from a single template constitutes a rare study in contemporary organic synthesis

Development of Gelatin Nanoparticle-Based Biodegradable Phototheranostic Agents: Advanced System to Treat Infectious Diseases

Rose bengal (RB)-conjugated and -entrapped gelatin nanoparticle (GNP)-based biodegradable nanophototheranostic (Bd-NPT) agents have been developed for the efficient antimicrobial photodynamic therapy. The study reveals that the use of gelatin nanoparticles could bypass the chemicals such as potassium iodide, EDTA, calcium chloride and polymyxin nonapeptide for the penetration of drug into the cell membrane to achieve antimicrobial activity. We demonstrated that the singlet oxygen generated by the biodegradable gelatin nanoparticles (BdGNPs) could damage the microbial cell membrane and the cell dies. The key features of the successive development of this work include the environmentally benign amidation of RB with GNPs, which was so far unexplored, and the entrapment of RB into the gelatin nanoparticles (GNP). The RB-GNP exhibited potent and broad-spectrum antimicrobial activity and could be useful in treating multi-drug-resistant microbial infections

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