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.

Synthesis of Metallo-Chromone Porphyrin Nano-Starch Sensitizers as Photodynamic Therapeutics for the Eradication of Enterococci Dental Pathogens.

Photodynamic therapy (PDT), as an advanced, alternative, and promising treatment, can inhibit dental pathogens. PDT employs the activation of photosensitizers via the light of a particular wavelength and molecular oxygen to inhibit dental pathogens. Herein, we present a comprehensive study on the synthesis and characterization of three chromone-porphyrins [Zn(II)-5-[4-chromone]-15-(4-phenyl)porphyrin (ZnCP), 5-[4-chromone]-15-(4-12 phenyl)porphyrin (DMCP), and Pd(II)-5-[4-chromone]-15-(4-phenyl)porphyrin (PdCP)]. Next, the computational study was also performed to establish the correlation between photophysical properties and theoretical calculations for those chromone-porphyrins using density functional theory and time-dependent density functional theory. Furthermore, chromone-porphyrins were encapsulated in starch nanoparticles to develop soluble nano-starch sensitizers (ZnCP-SNPs, DMCP-SNPs, and PdCP-SNPs) via the nanoprecipitation technique. Upon green light exposure, these nano-starch sensitizers exhibited excellent singlet oxygen generation ability. Moreover, final nanoformulations have been explored for pH responsiveness. Based on our intriguing findings, the chromone-porphyrin-loaded nano-starch sensitizers displayed great potential as prospective PDT to treat enterococci dental pathogens.

In Situ Nanoarchitectonics of a MOF Hydrogel: A Self-Adhesive and pH-Responsive Smart Platform for Phototherapeutic Delivery.

Metal-organic frameworks (MOFs) have dramatically changed the fundamentals of drug delivery, catalysis, and gas storage as a result of their porous geometry, controlled architecture, and ease of postsynthetic modification. However, the biomedical applications of MOFs still remain a less explored area due to the constraints associated with handling, utilizing, and site-specific delivery. The major drawbacks associated with the synthesis of nano-MOFs are related to the lack of control over particle size and inhomogeneous dispersion during doping. Therefore, a smart strategy for the in situ growth of a nano-metal-organic framework (nMOF) has been devised to incorporate it into a biocompatible polyacrylamide/starch hydrogel (PSH) composite for therapeutic applications. In this study, the post-treatment of zinc metal ion cross-linked PSH with the ligand solution generated the nZIF-8@PAM/starch composites (nZIF-8, nano-zeolitic imidazolate framework-8). The ZIF-8 nanocrystals thus formed have been found to be evenly dispersed throughout the composites. This newly designed nanoarchitectonics of an MOF hydrogel was found to be self-adhesive, which also exhibited improved mechanical strength, a viscoelastic nature, and a pH-responsive behavior. Taking advantage of these properties, it has been utilized as a sustained-release drug delivery platform for a potential photosensitizer drug (Rose Bengal). The drug was initially diffused into the in situ hydrogel, and then the entire scaffold was analyzed for its potential in photodynamic therapy against bacterial strains such as E. coli and B. megaterium. The Rose Bengal loaded nano-MOF hydrogel composite exhibited remarkable IC50 values within the range of 7.37 ± 0.04 and 0.51 ± 0.05 µg/mL for E. coli and B. megaterium. Further, reactive oxygen species (ROS) directed antimicrobial potential was validated using a fluorescence-based assay. This smart in situ nanoarchitectonics hydrogel platform can also serve as a potential biomaterial for topical treatment including wound healing, lesions, and melanoma.