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

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Porous silicon (pSi) is a versatile material for delivering biomacromolecules due to its tunable properties.
• Delivery efficiency is critically influenced by the carrier's interface during biological encounters, not just loading capacity.

Purpose of the Study:

• To review porous silicon-based delivery of various biologics (nucleic acids, peptides, proteins, antibodies) using an interface-centered framework.
• To analyze how interfacial changes impact delivery across different biological phases: extracellular, cellular entry, and intracellular processing.

Main Methods:

• Systematic review of literature on porous silicon for biomacromolecule delivery.
• Analysis through a phase-based, interface-centered framework, considering carrier state, cell entry mechanisms, and intracellular fate.

Main Results:

• Interfacial remodeling in biofluids and extracellular exposure significantly affect the carrier before cell contact.
• Cellular entry is governed by targeting, uptake pathways, and membrane interactions.
• Intracellular processing depends on endosomal escape, cargo destination, and integrity.

Conclusions:

• The primary delivery bottleneck varies with the biomacromolecule's mechanism of action.
• Key design principles include managing the outer interfacial state, matching cargo and carrier phases, and phase-appropriate validation.
• Porous silicon functions as a delivery scaffold where interfacial engineering is crucial for functional delivery and translational success.