In situ cellular hitchhiking of nanoparticles for drug delivery

Since the inception of the concept of "magic bullet", nanoparticles have evolved to be one of the most effective carriers in drug delivery. Nanoparticles improve the therapeutic efficacy of drugs offering benefits to treating various diseases. Unlike free drugs which freely diffuse and distribute through the body, nanoparticles protect the body from the drug by reducing non-specific interactions while also improving the drug's pharmacokinetics. Despite acquiring some FDA approvals, further clinical application of nanoparticles is majorly hindered by its limited ability to overcome biological barriers resulting in uncontrolled biodistribution and high clearance. The use of cell-inspired systems has emerged as a promising approach to overcome this challenge as cells are biocompatible and have improved access to tissues and organs. One of such is the hitchhiking of nanoparticles to circulating cells such that they are recognized as 'self' components evading clearance and resulting in site-specific drug delivery. In this review, we discuss the concept of nanoparticle cellular hitchhiking, highlighting its advantages, the principles governing the process and the challenges currently limiting its clinical translation. We also discuss in situ hitchhiking as a tool for overcoming these challenges and the considerations to be taken to guide research efforts in advancing this promising technology.