Side effects of the Conventionally used chemotherapies and the limited cell-permeability of the drugs owe to find out the most efficient strategies for the cancer treatment. In the recent years combi-nation of compounds with limited cell-permeability with efficient delivery systems to minimize side effects and enhance cell-permeability is the area of interest for the formulators. Cell penetrating peptides (CPPs) have the ability to cross the cell membrane which is the obstacle of the delivery of the various anticancer molecules. Limited cell-permeability of the drugs results into the low bioavailability which limits the biological application of the anticancer drugs. CPPs are able to internalize in nearly all cell types in vitro and in vivo, while the transport of cargos is virtually possible without any size restriction. Due to high specificity and low toxicity profile, pharmaceutical companies offer viable alternatives to small molecule therapeutics. In this review we have discussed the challenges of the cpp as drug delivery and the applications of the CPP as compared to other Conventionally used chemotherapies.

Keywords: Chemotherapetic agents, Cell penetrating peptides, Anticancer drugs.

Side effects of the Conventionally used chemotherapies and the limited cell-permeability of the drugs owe to find out the most efficient strategies for the cancer treatment. In the recent years combi-nation of compounds with limited cell-permeability with efficient delivery systems to minimize side effects and enhance cell-permeability is the area of interest for the formulators. Cell penetrating peptides (CPPs) have the ability to cross the cell membrane which is the obstacle of the delivery of the various anticancer molecules. Limited cell-permeability of the drugs results into the low bioavailability which limits the biological application of the anticancer drugs. CPPs are able to internalize in nearly all cell types in vitro and in vivo, while the transport of cargos is virtually possible without any size restriction. Due to high specificity and low toxicity profile, pharmaceutical companies offer viable alternatives to small molecule therapeutics. In this review we have discussed the challenges of the cpp as drug delivery and the applications of the CPP as compared to other Conventionally used chemotherapies.

Keywords: Chemotherapetic agents, Cell penetrating peptides, Anticancer drugs.

Cell-penetrating peptides (CPPs) are typically consist of 5–30 amino acids with the ability to cross the cell membrane for this CPPs have been used for a variety of applications [1].

cell-penetrating peptides (CPPs) correspond to short 30 residue synthetic peptides and are able to traverse biological membranes and to deliver numerous compounds including small molecules, nucleic acids, proteins, viruses, imaging agents and drugs inside the cells [1,2].

Typical short duration of action and lack of oral bioavailability limits the CPPs as pharmaceutical product. One of the true drawbacks of peptide drugs is the increased proteolytic instability compared to not only small molecules but also monoclonal antibody therapeutics. The modification of the peptide structure by acylation, PEGylation, unnatural amino acids or restricted conformation can largely remove this issue [3-14]. The introduction of D-amino acids instead of their L-amino acid configuration in CPP sequences represents a common strategy to protect peptides from degradation [12].

For peptide-based drug development, a compromise has to be found between the required peptide length and pharmacologically useful levels of receptor activation. The numerous variables include (i) the size and accessibility of ligand binding surfaces, (ii) possible induced fit; (iii) ligand stability and receptor residency time [14].

peptides are rapidly excreted through the kidney, serum stability studies are not representative of true turnover [14].

Development of a folate and tumor microenvironmentsensitive polypeptides dual-modified docetaxel-loaded nanostructured lipid carrier (F/TMSP-DTX-NLC) shows high encapsulation efficiency (>95%), sustainable release and targeted delivery manner. The enhancement in the cellular uptake and cytotoxic activity of F/ TMSP-DTX-NLC in KB, HT-1080, MCF-7 and A549 cells proved the correlation with folate receptor expression and MMP-2/9 secretion. The F/ TMSP-DTX-NLC significantly penetrate deeply into inner of multicellular tumor spheroids due to the function of cellpenetrating peptides. Finally, treatment with F/ TMSP-DTXNLC resulted in stronger antitumor efficacy and enhanced tumor cell apoptosis in KB tumor model in athymic nude mice [15,16].

In the another study in which the constructed a photoresponsive CPP termed pCPP and conjugated it to the NLC aiming at enhanced targeted tumor therapy. The Cellular experiments showed that pCPP-NLC exhibited significantly elevated light-dependent cellular accumulation in HT-1080 via clathrin-mediated endocytosis and macropinocytosis, and improved the cytotoxicity of PTX. Furthermore, the pCPP-NLC significantly could penetrate deeply into inner of multicellular tumor spheroids due to the function of Pcpp [17], This study demonstrates the application of CPP for efficient delivery of therapeutic agents for oncotherapy [17].

TAT-based targeted nanoparticles encapsulating DOX and ICG for combined chemo/photothermal/photodynamic therapy significantly increased the cellular DOX accumulation due to the electrostatic interaction between TAT peptide and HSPGs on surface of cell membrane [18]. The released rate of loaded DOX could also be promoted after NIR irradiation. Meanwhile, the ICG efficiently converted NIR light into violent heat and plentiful ROS. In vitro study confirmed that the cRGD@TAT-DINPs showed higher cytotoxicity on both MDA-MB-231 and A549 cells. These presented results provides a promising approach for high-efficient combined anticancer treatment [18].