Nanoengineered therapeutics for snakebite envenoming: Integrating recombinant antivenoms, targeted nanocarriers, nanobodies, toxin inhibitors, and translational challenges

Snakebite envenoming remains one of the most devastating neglected tropical diseases, causing an estimated 81,000–138,000 deaths and over 400,000 permanent disabilities annually, predominantly among rural populations in low- and middle-income countries. Despite the life-saving efficacy of conventional plasma-derived antivenoms, their therapeutic effect is often compromised by limited tissue penetration, delayed neutralization kinetics, immunogenicity, batch-to-batch variability, cold-chain dependence, and narrow species specificity. Recent advances in recombinant biologics, nanobody engineering, small-molecule toxin inhibitors, and nanomedicine formulation science are transforming the therapeutic landscape. However, the evidence base remains fragmented, and the field lacks a unified conceptual framework for integrating these modalities into clinically translatable multifunctional platforms. This review evaluates emerging nanoengineered therapeutic strategies for snakebite envenoming within a translational roadmap. The review examines the molecular basis of venom pathophysiology as a foundation for targeted intervention, evaluate the evolution from conventional to recombinant antivenoms, and analyze how nanocarrier technologies can overcome pharmacokinetic and biodistribution limitations of next-generation biologics. The review also analyzed nanobodies, small-molecule inhibitors, and their potential for nanoformulation-enhanced delivery, before proposing an integrated therapeutic paradigm that combines rapid toxin suppression, specific antibody neutralization, and targeted transport within stimuli-responsive nanoplatforms. The review also addresses the biological evaluation methodologies, manufacturing scale-up, regulatory harmonization, and future research priorities necessary to advance these innovations from bench to bedside.