Emerging strategies in exosome engineering: From cellular preconditioning to hybridization for targeted therapeutics

Exosomes are nanosized extracellular vesicles that originate from all cell types. They have a precious role in intercellular communication and therapeutic delivery. Exosomes are considered attractive candidates because of their innate biocompatibility, low immunogenicity, and ability to transport bioactive molecules across biological barriers. However, some challenges are related to the clinical application of native exosomes. These challenges have led to advances in the engineering of exosomes. Surface modifications, cargo loading techniques, and hybridization with synthetic materials are some examples of these modifications. This review article explores innovative strategies to enhance the therapeutic potential of these exosomes. It focuses on modifying stem cells during the culture phase using techniques such as hypoxic preconditioning, chemical stimulation, and biophysical stimulation, which have been shown to optimize the quantity and biological activity of exosomes. Additionally, post-production modifications, including surface functionalization, hybridization with synthetic materials, and cargo enhancement, are being investigated for their role in improving the stability, targeting specificity, and therapeutic efficacy of exosomes. Together, these insights offer a roadmap for realizing the full potential of exosomes as next-generation delivery tools in nanomedicine.