Silk Proteins in Cancer Nanomedicine: Drug Delivery, Tumour Targeting and Emerging Theranostic Platforms

Silk proteins derived from the domesticated silkworm Bombyx mori, from wild silkmoths, and from spiders have moved from their long-standing role as surgical sutures towards a central position in experimental cancer nanomedicine. Their aqueous processability, tunable β-sheet crystallinity, proteolytic degradability and generally modest immunogenicity allow a single material family to be reconfigured as nanoparticles, films, hydrogels, microspheres and microneedles, each capable of carrying small-molecule cytotoxic agents, nucleic acids, proteins and inorganic payloads. This review examines the state of knowledge on silk-based carriers for oncology and offers a critical rather than descriptive synthesis. Evidence was assembled from open scholarly databases and verified against authoritative bibliographic records. The analysis is organised around the material platform and its biological interface, the mechanisms of drug loading and stimulus-responsive release, passive and active tumour targeting, and multimodal theranostic constructs that combine therapy with imaging or immunomodulation. Across these themes the preclinical evidence is internally consistent in showing that silk carriers can increase payload stability, modulate release kinetics through controllable crystallinity, and exploit the acidic and enzyme-rich endolysosomal compartment to trigger drug liberation. The strength of this evidence is nonetheless constrained by heavy reliance on in vitro models and small, heterogeneous rodent studies, by inconsistent physicochemical reporting, and by an almost complete absence of pharmacokinetic and immunological data for systemically administered particles. Active targeting and recombinant silk engineering show genuine mechanistic promise, yet head-to-head comparisons against clinically validated carriers are rare. Localised silk depots for post-surgical and intratumoural therapy appear closer to translation than circulating nanoparticles. The principal unresolved questions concern manufacturing reproducibility, the behaviour of silk particles in the circulation, the durability of targeting under physiological protein adsorption, and the regulatory pathway for a natural, batch-variable biopolymer. Progress will depend less on proliferating new formulations than on standardised characterisation, rigorous in vivo pharmacology and disciplined comparison with existing nanomedicines.