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International Journal of Pharmacology

Year: 2017  |  Volume: 13  |  Issue: 7  |  Page No.: 677 - 689

Cell Penetrating Peptides: Biomedical/Therapeutic Applications with Emphasis as Promising Futuristic Hope for Treating Cancer

Rekha Khandia, Ashok Munjal, Arvind Kumar, Gaurav Singh, Kumaragurubaran Karthik and Kuldeep Dhama


The intrinsic property of Cell Penetrating Peptides (CPP) is to deliver various molecules including nucleic acids, large plasmids, therapeutic drugs, imaging molecules, liposomes, nano-molecules to various cell and tissues, which indicates about the potential of CPP as therapeutic vehicle molecules. These are easy to prepare, well characterized, versatile and have ability to link with bioactive cargo through covalent and non-covalent bonds. The interaction between cargo and CPP is highly dependent on physiochemical properties of CPP including size, pH and presence of basic residues in the carrier peptide. Primary mechanism of transport of CPP is endocytosis; however, evidences of endocytosis independent mechanisms including carpet model, inverted micelle model, barrel stave pore model and toroidal pore model are also present. Though, the natural CPP are often non- selective and passive, these may be tuned to become specific and targeted by conjugating them with functional groups and chemicals. In fact several natural CPPs such as penetratin, Tat, polyarginies etc have been modified to achieve maximum penetration and desired characters. Linear CPPs may be brought into multi-branched topology to give dendrimeric structures having more cell penetrating capacity, lower toxicity and hemolysis and higher serum stability. Site-specific targeting of CPP might be helpful in achieving several goals including enhancement in protein expression, gene silencing, formation of pleuripotent cells, reduction in inflammation and apoptosis, trans-epithelial transport, neuroprotection, ischemia treatment, treating insulin disorders, delivery of nucleic acids and agricultural pest control. The present review encompasses the detailed information regarding different modes of entry of CPP inside the cells, designing and classes of such peptides, along with theirs versatile therapeutic applications.

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