Integrating Nanomaterials with Extracellular Vesicles: Engineering Strategies and Translational Perspectives.

Extracellular vesicles (EVs), particularly stem cell-derived exosomes, serve as vital natural nanocarriers in regenerative medicine, immune modulation, and targeted drug delivery due to their innate ability to transport bioactive cargo across complex biological barriers. Despite this potential, the therapeutic efficacy of native EVs is frequently constrained by intrinsic limitations such as rapid systemic clearance, low loading efficiency, limited targeting specificity, and significant manufacturing hurdles. Integrating engineered nanomaterials provides a powerful synergistic strategy to enhance EVs systems through sophisticated engineering that improves structural stability, maximizes cargo loading, and introduces multifunctional capabilities like real-time imaging and stimuli-responsive release. The objective of this review is to systematically analyze rational design principles for nano-EV hybrid systems while evaluating the critical barriers to their clinical translation. Key themes discussed include diverse engineering strategies-ranging from surface functionalization to scaffold-based delivery-alongside therapeutic applications in oncology and regenerative medicine, safety assessments, and production standardization. Ultimately, these advanced nano-EV platforms signify a transformative direction for next-generation nanomedicine, offering intelligent and scalable solutions for precise, clinically translatable therapeutics.