Silk Sericin/Fibroin Composite Drug Delivery Systems for Lung Cancer: Mechanistic Rationale, Potential Functional Complementarity, and Future Perspectives.

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 behavior 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. This review compares representative SF-based, SS-based, and SS/SF composite systems, focusing on pulmonary targeting, responsive drug release, tumor-microenvironment interactions, and translational considerations. Selected SS/SF composites have demonstrated combinations of geometry-associated pulmonary accumulation, environment-associated release, prolonged local retention, and immune- or tumor-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. Future progress requires standardized 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.