Cell-penetrating peptides (CPPs): an overview of applications for improving the potential of nanotherapeutics

In the field of nanotherapeutics, gaining cellular entry into the cytoplasm of the target cell continues to be an ultimate challenge. There are many physicochemical factors such as charge, size and molecular weight of the molecules and delivery vehicles, which restrict their cellular entry. Hence, to dodge such situations, a class of short peptides called cell-penetrating peptides (CPPs) was brought into use. CPPs can effectively interact with the cell membrane and can assist in achieving the desired intracellular entry. Such strategy is majorly employed in the field of cancer therapy and diagnosis, but now it is also used for other purposes such as evaluation of atherosclerotic plaques, determination of thrombin levels and HIV therapy. Thus, the current review expounds on each of these mentioned aspects. Further, the review briefly summarizes the basic know-how of CPPs, their utility as therapeutic molecules, their use in cancer therapy, tumor imaging and their assistance to nanocarriers in improving their membrane penetrability. The review also discusses the challenges faced with CPPs pertaining to their stability and also mentions the strategies to overcome them. Thus, in a nutshell, this review will assist in understanding how CPPs can present novel possibilities for resolving the conventional issues faced with the present-day nanotherapeutics.