A Combined Phyto- and Photodynamic Delivery Nanoplatform Enhances Antimicrobial Therapy: Design, Preparation, In Vitro Evaluation, and Molecular Docking

Microbial combating is one of the hot research topics, and finding an alternative strategy is considerably required nowadays. Here, we report on a developed combined chemo- and photodynamic delivery system with a core of zinc oxide nanoparticles (ZnO NPs), porphyrin photosensitizer (POR) connected to alginate polymer (ALG), and berberine (alkaloid natural agent, BER) with favorable antimicrobial effects. According to the achieved main designs, the results demonstrated that the loading capacity and entrapment efficiency reached 22.2 wt % and 95.2%, respectively, for ZnO@ALG-POR/BER nanoformulation (second design) compared to 5.88 wt % and 45.1% for ZnOBER@ALG-POR design (first design). Importantly, when the intended nanoformulations were combined with laser irradiation for 10 min, they showed effective antifungal and antibacterial action against <i>Candida albicans</i>, <i>Escherichia coli</i>, and <i>Staphylococcus aureus</i>. Comparing these treatments to ZnO NPs and free BER, a complete (100%) suppression of bacterial and fungal growth was observed by ZnO@ALG-POR/BER nanoformulation treated <i>E. coli</i>, and by ZnOBER treated <i>C. albicans</i>. Also, after laser treatments, most data showed that <i>E. coli</i> was more sensitive to treatments using nanoformulations than <i>S. aureus</i>. The nanoformulations like ZnOBER@ALG-POR were highly comparable to traditional antibiotics against <i>C. albicans</i> and <i>E. coli</i> before laser application. The results of the cytotoxicity assessment demonstrated that the nanoformulations exhibited moderate biocompatibility on normal human immortalized retinal epithelial (RPE1) cells. Notably, the most biocompatible nanoformulation was ZnOBER@ALG-POR, which possessed ∼9% inhibition of RPE1 cells compared to others. High binding affinities were found between all three microbial strains' receptor proteins and ligands in the molecular docking interaction between the receptor proteins and the ligand molecules (mostly BER and POR). In conclusion, our findings point to the possible use of hybrid nanoplatform delivery systems that combine natural agents and photodynamic therapy into a single therapeutic agent, effectively combating microbial infections. Therapeutic efficiency correlates with nanoformulation design and microorganisms, demonstrating possible optimization for further development.