Biohybrid nanocarriers for targeted drug delivery by integrating biological interfaces with synthetic platforms for site-specific therapeutics

Biohybrid nanocarriers (BHNs) are a fast-moving new horizon in targeted drug delivery, merging the biological complexity of naturally occurring systems like exosomes, bacterial outer membrane vesicles, red blood cell membranes, and other cell-derived vesicles with the structural versatility and functional adaptability of synthetic nanomaterials. This combined strength allows BHNs to be endowed with enhanced biocompatibility, extended systemic circulation, minimized immunogenicity, and highly specific targeting properties. The objective of this review is to achieve a detailed and critical overview of recent developments in BHN platforms, highlighting their architectural diversity, drug-loading strategies, functional mechanisms, and wide therapeutic utility. BHNs are gaining attention for their promise in the therapy of cancer, neurodegenerative disorders, infectious diseases, and in next-generation vaccine delivery. RNA and protein delivery engineered exosomes, immune evasion, homotypic targeting cell membrane-coated nanoparticles, and smart hydrogels for responsive and localized drug release. These systems also provide multifunctionality through the co-delivery of therapeutic and imaging probes, facilitating in vivo tracking and theranostic applications. Their biomimetic design facilitates tissue regeneration, immune modulation, and better pharmacokinetics, with customizable platforms available for patient-specific therapy. The combination of biologic and synthetic components in BHNs is of transformative value for shaping safer, wiser, and more powerful nanomedicine approaches to personalized healthcare.