Bioinspired and Biomimetic Nanocarriers: Advances in Exosomes and Cell-Membrane-Coated Systems for Therapeutic...

The translation of nanomedicine from bench to bedside has been thwarted by the limitations of conventional synthetic nanoparticles including rapid mononuclear phagocyte system (MPS) clearance, lack of target specificity, immunogenicity and poor intracellular delivery. To overcome these limitations, bioinspired and biomimetic nanocarriers are emerging as the next generation of therapeutic platforms. Bioinspired systems replicate the core biological design principles with engineered synthetic materials and biomimetic platforms use natural biological components such as cell membranes and extracellular vesicles. We herein review recent advances in bioinspired design strategies including hybrid bio-synthetic systems, and two major classes of biomimetic nanocarriers; (1) cell membrane-coated nanoparticles (CM-NPs), focusing on self-assembly approaches and their improved features over conventional fabrication methods, and (2) exosomes and extracellular vesicles (EVs), including engineered exosomes, membrane-derived vesicles, and core-shell hybrid nanocarriers. The biogenesis and isolation of exosomes and strategies for loading drugs into exosomes are discussed in depth. In particular, homotypic targeting, CD47 surface protein-mediated immune evasion, and therapeutic drug release in response to the tumor microenvironment are highlighted. Therapeutic applications of biomimetic nanocarriers in cancer, gene delivery (siRNA, mRNA, CRISPR-Cas9), neurological disorders and inflammatory diseases are covered in detail. We then discuss the challenges to translation including scalability, lot-to-lot batch reproducibility, storage stability, immunogenicity and regulatory hurdles. For the future, we discuss the role of artificial intelligence in the design of nanocarriers and personalized nanomedicine. This review outlines the advantages and disadvantages of biomimetic nanocarriers to aid in the rational design of nanomedicine for clinical translation.