Concentration-Dependent Anticancer Effects of Melittin-Functionalized Nanomaterials

Melittin-functionalized nanoparticles have emerged as a strategy to harness the potent anticancer activity of melittin while mitigating its narrow therapeutic window. Across diverse nanocarrier platforms, biological outcomes are highly dependent on the effective melittin concentration presented to tumour cells. This review systematically examines concentration-dependent anticancer effects of melittin-functionalized nanoparticles, focusing on quantitative dose–response metrics such as IC50 values, shifts in cytotoxic potency relative to free melittin, and concentration-linked safety margins. Along with some aspects concerning the molecular mechanisms of melittin, this review synthesizes evidence from preclinical studies to analyze how nanoparticle functionalization reshapes the concentration–effect relationship governing anticancer efficacy. This review concluded that there are three concentration regimes that govern the molecular outcome in tumours treated with melittin and melittin-functionalised nanomaterials. Collectively, the data demonstrate that nanoparticle association typically attenuates melittin’s intrinsic lytic potency, requiring higher nominal concentrations to achieve cytotoxicity, while simultaneously enabling tumour-selective re-potentiation through targeting, activation, or intracellular release mechanisms. These concentration-dependent phenomena define the translational limits and opportunities of melittin-based nanomedicines.