Advanced extracellular vesicle therapeutics: From molecular engineering to intelligent devices

Area of Science:

• Biomaterials Science
• Nanomedicine
• Cell Biology

Background:

• Extracellular vesicles (EVs) are potent biologics with therapeutic potential.
• Clinical translation is limited by poor target engagement, rapid clearance, and uncontrolled in vivo release.
• Existing EVs lack sustained, site-specific activity crucial for effective therapy.

Purpose of the Study:

• To review advances in engineering EVs and delivery systems for improved therapeutic efficacy.
• To explore strategies for enhancing EV target accumulation, retention, and controlled release in vivo.
• To provide a framework for developing programmable and pathology-adaptive EV therapeutics.

Main Methods:

• Molecular engineering of EVs via donor-cell modification and chemical tailoring.
• Development of intelligent device-based delivery systems including hydrogels, bioelectronic interfaces, and microcarriers.
• Integration of EV engineering with biomaterial-based delivery strategies.

Main Results:

• Molecular engineering enhances EV intrinsic properties, stability, and cargo loading.
• Device-based technologies provide protection, programmed release, and improved tissue accumulation.
• Combined strategies address limitations in EV target engagement, clearance, and in vivo behavior.

Conclusions:

• Engineering EVs and their delivery environments offers a unified approach to overcome translational barriers.
• Programmable and pathology-adaptive EV therapeutics can be developed through combined strategies.
• These advances pave the way for precise, durable, and scalable EV-based medicines.