Silk sericin/fibroin composite drug delivery systems for lung cancer: mechanistic Rationale, potential functional complementarity, and future perspectives.

OBJECTIVES: Silk fibroin (SF) and silk sericin (SS) are promising biomaterials for lung cancer drug delivery because of their biocompatibility, biodegradability, and versatile processing. SF-based systems can provide structural stability and controlled or prolonged release, although release behaviour depends on drug properties, loading strategy, secondary structure, and formulation architecture. Engineered SS-containing systems may contribute hydrophilicity, formulation-dependent environmental responsiveness, and biologically relevant interactions, but SS-rich formulations can show limited structural robustness.

METHODS: This review compares representative SF-based, SS-based, and SS/SF composite systems, focusing on pulmonary targeting, responsive drug release, tumour-microenvironment interactions, and translational considerations.

RESULTS: Selected SS/SF composites have demonstrated combinations of geometry-associated pulmonary accumulation, environment-associated release, prolonged local retention, and immune- or tumour-microenvironment-related activity. However, evidence for SF/SS complementarity remains limited and heterogeneous, with major differences in silk source, processing, composition, cargo, administration route, and disease model. Accordingly, this complementarity should be regarded as a provisional conceptual framework rather than a universally validated mechanism.

CONCLUSIONS: Future progress requires standardised materials, composition-matched comparisons, formulation-specific safety assessment, reproducible manufacturing, and clinically relevant delivery strategies to determine whether SS/SF composites provide measurable advantages over simpler silk-based or non-silk systems.