Microbial Nanofactories in Cancer Nanomedicine: Harnessing Bacillus subtilis for Green Synthesis of Silver Nanoparticles in Cancer Therapy

Abstract

The global pursuit of sustainable nanomedicine has accelerated interest in microbial systems as eco-friendly nanofactories capable of producing biologically compatible metal nanoparticles. This review critically explores the role of Bacillus subtilis in the green synthesis of silver nanoparticles (AgNPs) and their therapeutic applications in hepatocellular carcinoma (HCC). Literature from 2010–2025 was systematically screened across PubMed, Scopus, and Web of Science using predefined inclusion criteria focused on B. subtilis–mediated AgNP synthesis and anticancer efficacy. The evidence demonstrates that B. subtilis extracellular enzymes, particularly nitrate reductases and oxidoreductases, facilitate the reduction of Ag⁺ ions to Ag⁰, producing nanoparticles with high stability, spherical morphology (10–50 nm), and a strong negative surface charge. These biologically capped AgNPs exert selective cytotoxicity in hepatic cancer models (HepG2, Huh7) through enhanced reactive oxygen species (ROS) generation, mitochondrial depolarization, caspase-3/9 activation, and apoptosis, while maintaining minimal toxicity to normal hepatocytes. Mechanistic studies reveal modulation of NF-κB, COX-2, mTOR, and AMPK pathways, underpinning their multifaceted anticancer effects. Compared with chemically synthesized nanoparticles, B. subtilis–derived AgNPs exhibit superior biocompatibility, reduced aggregation, and environmental sustainability. Despite promising preclinical findings, translational challenges persist, including synthesis variability, incomplete toxicological profiling, and limited in vivo validation. Clinically, Bacillus subtilis–based biogenic AgNPs offer a novel, sustainable approach to liver cancer nanotherapy with potential for integration into targeted drug delivery and redox-modulating treatment strategies. Future research should focus on genetic optimization of microbial strains, process standardization, and comprehensive pharmacokinetic studies to enable safe clinical translation of microbial nanomedicine for hepatic oncology