Snake venom toxins in cancer therapy: advances in targeted delivery and peptide design

Snake venom represents a potent biological arsenal of cytotoxic compounds. Venom proteins and peptides, including disintegrins, venomous enzymes, three-finger toxins, and serine proteases, have garnered attention as effective anticancer agents. Despite their efficacy at nano- or micromolar concentrations, non-standardized mixtures often limit their therapeutic utilization, necessitating fractionation to minimize side effects. This review examines the antitumor potential of snake venom and its constituent proteins and peptides through a literature search in NCBI PubMed. We highlight the antitumor efficacies of venom polypeptides by correlating them with IC₅₀ values across various cell lines, demonstrating micromolar cytotoxic concentrations. The review encompasses several key areas: whole venom antitumor efficacy, mechanisms of action of individual proteins and peptides, fractionation and purification methods, cytotoxic effects of low molecular weight peptides, and delivery system approaches utilizing peptide sequences as cell-penetrating mechanisms alongside liposomes and nanoparticles for enhanced polypeptide toxicity. Given that cilengitide contains an RGD sequence analogous to disintegrins and targets integrins, we provide a dedicated analysis of its anticancer potential and clinical trial outcomes. Clinical evidence indicates the necessity for further investigation into the synergistic effects of cilengitide with established chemotherapeutic agents. The scientific data reviewed demonstrate that antimetastatic properties constitute the most extensively studied mechanism of venom polypeptides. This review underscores the therapeutic promise of venom-derived polypeptides while emphasizing the critical need for advanced delivery systems and rigorous clinical validation to translate these findings into viable cancer therapeutics.