Problem-driven engineering of porous silicon particles: from fundamental challenges to multifunctional biomedical platforms

Porous silicon nanoparticles (pSiNPs) occupy a unique position in the field of biomedical nanomaterials. Their degradable silicon framework, tunable porosity, intrinsic photoluminescence in suitably prepared materials, and diverse surface functionalization options make them attractive candidates for drug delivery, bioimaging, and therapeutic applications. However, these material attributes alone do not establish the performance or safety of individual formulations, which require evaluation in relation to their surface chemistry, coatings, payloads, and intended biological use. This review examines a decade of research by our groups addressing five interconnected engineering challenges: surface functionalization, cargo retention and release control, application-specific formulation design, biological safety evaluation, and particle production. We describe the development of novel surface chemistries, including thermal dehydrocoupling, heterocyclic silane functionalization, and microwave-induced Si–S bond formation, which expand the available toolkit for surface engineering. We then discuss inorganic silicate sealing and hybrid coatings as strategies for improving cargo retention and release control while introducing additional imaging or therapeutic functions. Selected imaging and disease-focused studies illustrate the adaptability of porous silicon-based formulations. We also discuss single-cell transcriptomic analysis in zebrafish as an approach to formulation-specific biological evaluation and describe engineering advances in gram-scale particle preparation. Chemical versatility and application are distinguished from biological generalizability: surface modification and coating strategies must balance cargo retention, release, and carrier degradation, while their biological effects require formulation-specific evaluation. We critically examine these trade-offs, the scope of available safety evidence, and the remaining requirements for long-term assessment and reproducible manufacturing. The narrative is organized not as a catalog of results but as a series of deliberate choices made in response to specific limitations, highlighting demonstrated capabilities, unresolved trade-offs, and the validation required to guide further biomedical development. In this review, five structural problems that hindered pSiNP translation are systematically resolved through a cumulative, problem-driven engineering strategy