Polymeric micelles functionalized with cell penetrating peptides as potential pH-sensitive platforms in drug delivery for cancer therapy: A review

Abstract Improving the intrinsic pharmacodynamics or pharmacokinetic of drugs is regarded as a crucial step in developing potential drug therapies. In this context, the development of nanostructured-based drug delivery systems (DDSs) responsive to exogenous or endogenous stimuli demonstrate an outstanding platform to clinical applications. Polymeric micelles (PM)-based DDSs are often modified with selective short peptides like cell penetrating peptides (CPPs) for highly efficient cellular internalization. In this review, we discussed recent achievements in the design and development of nanoscale pH-responsive micelles modified with CPPs to provide controlled drug release in the tumor cells. An overview on the application of micelles, especially PMs as promising engineered nanocarriers to combine pharmaceutical agents with CPPs are presented. Afterwards, the peptide-based transfection method as one of the promising approaches for drug delivery and therapeutic agents was explained. Subsequently, conjugation of pH-responsive micelles with CPPs as a novel DDS in cancer therapy was surveyed. Finally, the current challenges and future application of stimuli-sensitive nanoplatforms conjugated with CPP were discussed. In conclusion, the application of controlled delivery using pH-sensitive PMs-based DDSs conjugated with peptides can be considered as a potential approach to improve the therapeutic index of anticancer drugs.