Abstract
Cell penetrating peptides (CPP) are able cross the membrane and to transport cargos, presenting a great potential in drug delivery and diagnosis. In this paper, we have identified novel natural or synthetic CPPs. We have validated their rapid and efficient time and dose-dependent penetration, the absence of toxicity, the intracellular localization and the stability to proteases degradation, one of the main bottlenecks of peptides. Moreover, we have associate a cargo (an interfering peptide blocking the association of the serine/threonine phosphatase PP2A to its inhibitor, the oncogene SET) to the new generated shuttles and showed that they new bi-functional peptides keep the original properties of the shuttle and, in addition, are able to induce apoptosis due to the properties of the cargo. The CPPs identified in this study have promising perspectives for future anti-cancer drug delivery.
Highlights
One of the obstacles to the use of therapeutic molecules having intracellular targets is they low penetration through the membrane
We have associate a cargo to the new generated shuttles and showed that they new bi-functional peptides keep the original properties of the shuttle and, in addition, are able to induce apoptosis due to the properties of the cargo
We have recently published the use of a cell penetrating peptides (CPP) named Mut3DPT [15, 16]
Summary
One of the obstacles to the use of therapeutic molecules having intracellular targets is they low penetration through the membrane. The best way to solve this problem is the use of cell penetrating peptides (CPP), molecules capable to cross the cell membrane. They can transport a great variety of cargos into the cell in terms of size and nature [1,2,3]. Several studies tried to design novel CPP with greater efficacy and selectivity. Since Tat (CPP with high number of basic residues), Wender and co workers showed that poly Arginine peptide is an efficient CPP [4]. Several groups have synthesized oligo arginines of different sizes and studied their internalization and efficiency [5]
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