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

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.