Engineered exosomes and hybrid nanosystems for cancer theranostics: mechanisms, strategies, and translational hurdles

Exosomes (EXOs) have garnered significant attention as natural nanoparticles (NPs) for cancer therapy. EXOs having an endogenous origin offer several benefits, including biocompatibility, reduced immunogenicity, deeper penetration into tumor tissues, and targeted delivery due to homing abilities, thereby overcoming the limitations associated with artificial NPs. Additionally, they facilitate cellular interaction by transferring various biomolecules, such as proteins, nucleic acids, etc., thus suggesting their potential as a drug delivery vehicle. EXOs can be engineered in order to enhance their therapeutic payload capacity and targeting abilities. Hybrid nanosystems, a type of EXOs engineering, consist of NPs combined with EXOs, thus capitalizing on the strengths of both artificial and natural nanocarriers and overcoming the limitations of using each of them alone. This review article explains the mechanisms underlying EXOs-mediated cancer progression as well as the role of engineered EXOs (eEXOs) as therapeutic drug delivery vehicles. Moreover, it provides a comparative analysis of different strategies utilized for EXOs’ engineering. We discuss the potential advantages of the EXO-NPs hybrid system in cancer theranostics along with a comparative analysis of hybrid systems. Lastly, the challenges associated with translating EXOs into clinical settings and future trends are also discussed.