Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers.

The complex physiological and pathological conditions form barriers against efficient drug delivery. Cell penetrating peptides (CPPs), a class of short peptides which translocate drugs across cell membranes with various mechanisms, provide feasible solutions for efficient delivery of biologically active agents to circumvent biological barriers. After years of development, the function of CPPs is beyond cell penetrating. Multifunctional CPPs with bioactivity or active targeting capacity have been designed and successfully utilized in delivery of various cargoes against tumor, myocardial ischemia, ocular posterior segment disorders, etc. In this review, we summarize recent progress in CPP-functionalized nano-drug delivery systems to overcome the physiological and pathological barriers for the applications in cardiology, ophtalmology, mucus, neurology and cancer, etc. We also highlight the prospect of clinical translation of CPP-functionalized drug delivery systems in these areas.