Rationale: A cell-specific delivery vehicle is required to achieve gene editing of the disease-associated cells, so the hereditable genome editing reactions are confined within these cells without affecting healthy cells. A hybrid exosome-based nano-sized delivery vehicle derived by fusion of engineered exosomes and liposomes will be able to encapsulate and deliver CRISPR/Cas9 plasmids selectively to chondrocytes embedded in articular cartilage and attenuate the condition of cartilage damage.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications. Graphical Abstract

Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities and reduced off-target effects is crucial. CNS-targeted drug carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, and neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in CNS-targeted drug delivery, because of their intrinsic stability, biocompatibility, inherent homing capability, and the ability to penetrate through biological barriers, including the blood-brain barrier. Among these CDNs, extracellular vesicles and exosomes are the most studied because their surface can be engineered and modified to cater to brain targeting. In this review, we focus on the application of CDNs in brain-targeted drug delivery to treat neurological diseases. We cover recently developed methods of exosome derivation and engineering, including exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, and envelope protein nanocages. Finally, we discuss the limitations and project the future development of the CDN-based brain-targeted delivery systems, and conclude that engineered CDNs hold great potential in the treatment of neurological diseases.

Articular cartilage repair is a critical issue in osteoarthritis (OA) treatment. The insulin-like growth factor (IGF) signaling pathway has been implicated in articular cartilage repair. IGF-1 is a member of a family of growth factors that are structurally closely related to pro-insulin and can promote chondrocyte proliferation, enhance matrix production, and inhibit chondrocyte apoptosis. Here, we reviewed the role of IGF-1 in cartilage anabolism and catabolism. Moreover, we discussed the potential role of IGF-1 in OA treatment. Of note, we summarized the recent progress on IGF delivery systems. Optimization of IGF delivery systems will facilitate treatment application in cartilage repair and improve OA treatment efficacy.