Porous Silicon for Biomacromolecule Delivery: From Extracellular Interfaces to Intracellular Function

ABSTRACT

Porous silicon (pSi) is a promising platform for biomacromolecule delivery because its pore structure, surface chemistry, degradation behavior, and outer interfaces are readily tunable. Yet delivery performance is rarely determined by loading alone. It is more often shaped by how the biologically encountered interface changes from extracellular exposure to cell entry and intracellular processing. This review examines pSi‐based delivery of nucleic acids, peptides, proteins, antibodies, and related biologics through a phase‐based, interface‐centered framework. We first consider how loading‐compatible stabilization, biofluid‐mediated interfacial remodeling, and extracellular exposure control influence the carrier state before cell contact. We then examine how targeting, uptake routing, membrane fusion, and barrier access shape entry, followed by how endosomal escape, cargo destination, cargo integrity, and function‐linked readouts determine intracellular availability. Comparison across cargo classes shows that the dominant bottleneck shifts with the cargo's mode of action, whereas several design principles recur across systems, particularly the biologically presented outer state, cargo–phase matching, and phase‐appropriate validation. In this view, pSi is best understood not simply as a porous host matrix, but as a delivery scaffold whose interfacial design strongly influences functional biomacromolecule delivery and translational potential.