Anticancer Mechanisms of Green-Synthesised Silver Nanoparticles: From Sustainable Synthesis to Advanced Nanoplatforms and Therapeutic Translation

Abstract

The green-synthesised silver nanoparticles (AgNPs) have become great interest as promising nanotherapeutic agents for cancer therapy owing to their eco-friendly synthesis, better biocompatibility, anticancer activity and less toxicity than chemically synthesised nanoparticles. However, there is fragmented perception of mechanistic connection between their physicochemical properties, cellular uptake, molecular pathways and therapeutic efficacy. This review critically summarises the current understanding of green-synthesised AgNPs with particular emphasis on their physico-chemical properties, cellular uptake, molecular mechanism of anticancer activity, therapeutic applications and translational obstacles. A structured literature review was conducted using peer-reviewed studies from major scientific databases, focusing on recent mechanistic, in vitro, in vivo, and nano-formulation based evidence related to AgNP anticancer activity. The current evidences revealed that plant-mediated synthesis is the most prevalent method to synthesise biocompatible AgNPs that are highly stable with better selectivity towards cancer cells. AgNPs induce anticancer effects by inducing reactive oxygen species (ROS)-mediated cytotoxicity and modulating key signalling pathways leading to apoptosis, autophagy, cell-cycle arrest, anti-angiogenic and anti-metastatic effects enhancing controlled and targeted drug delivery. However, challenges such as synthesis heterogeneity, limited long-term toxicological data and lack of standardisation remain barriers to translation. This review provides technology-oriented and mechanistic perspective by connecting sustainable synthesis with nanoparticle design, physicochemical engineering, cellular uptake, molecular signalling, surface functionalisation, polymeric nanocomposites, hybrid nanoplatforms, targeted delivery, controlled drug-release and theronostic applications. The review further evaluates current research trends, biological-synthesis platforms, cancer-specific responses, technological limitations and barrier to clinical translational, thereby providing a framework for development of next-generation green-synthesised AgNPs.