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

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

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

Bioinspired Nanotheranostic Agents: Synthesis, Surface Functionalization, and Antioxidant Potential

Bioinspired synthesis of nanomaterials is highly advantageous as a natural and cost-effective resource. Development of noble metal nanotheranostic agents was achieved through bioinspired synthetic routes. These biosynthesized nanoparticles were characterized by various analytical techniques including absorption spectroscopy, FTIR and electron microscopy (SEM and TEM). A large number of medicinal plants were screened, among which <i>Potentilla fulgens</i> (PF, vajradanti) and <i>Camellia sinensis</i> (CS, green tea) were found to produce nanomaterials with higher yields. Plant (PF and CS) mediated metallic nanoparticles had added advantage of metal reduction and simultaneous phytochemical capping over chemically synthesized procedures, which require multiple reagents. Antioxidant potential of the nanomaterials was determined by in vitro antioxidant assays confirming substantial antioxidant properties, which was due to the presence of phytochemicals on the nanoparticle surface. Flavonoids and catechins on the nanomaterial surface served as the supplier of hydroxyl groups for further derivatization. The surface of the nanoparticles was engineered by conjugating imaging and therapeutic moieties, resulting in the formation of theranostic nanoagents. The multimodal agents were characterized and the extent of drug loading was determined to validate the efficacy of those nanoconjugates. These bioinspired multimodal nanoprobes can serve as essential diagnostic and therapeutic tools in ongoing biomedical research