The surface-first paradigm: Engineering nanocarriers for infection-responsive drug delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Traditional nanocarrier research focused on payload optimization, neglecting surface interactions.
• Emerging health challenges necessitate a shift towards advanced nanocarrier surface engineering.
• Conventional surface modifications like PEGylation have limitations in complex biological environments.

Purpose of the Study:

• To propose a surface-first framework for nanocarrier engineering.
• To highlight next-generation surface modifications like zwitterionic coatings and platelet-cloaked nanoparticles.
• To demonstrate the potential of surface chemistry in triggering drug release at specific sites.

Main Methods:

• Critical evaluation of conventional surface modifications.
• Spotlighting zwitterionic coatings and platelet-cloaked nanoparticles.
• Using infection-responsive systems as case studies for surface-triggered release.

Main Results:

• Surface-first engineering improves nanocarrier pharmacokinetics and biodistribution.
• Surface chemistry enables precision triggering of drug release (e.g., pH-activated charge reversal, MMP-cleavable linkers).
• Next-generation stealth and targeting strategies are exemplified by zwitterionic and platelet-cloaked nanoparticles.

Conclusions:

• A surface-first approach is essential for advancing targeted therapy.
• Standardized characterization, modular manufacturing, and theranostic interfaces are crucial for clinical translation.
• Co-design of nanocarrier core and surface enables mechanism-based controlled release.