Uptake Mechanism and Direct Translocation of a New CPP for siRNA Delivery

• DOI: 10.1021/acs.molpharmaceut.6b00030
• Publication Date: 2016-03-03T13:49:01Z
• Authors: Ran Pan; Wen Xu; Yong Ding; Sheng Lu; P. Chen
• Keywords: Internalization; Cell-penetrating peptide

Since their development, cell-penetrating peptides (CPPs) have been used as delivery vehicles for various genetic or therapeutic agents; however, the uptake mechanisms of CPPs and details are still unclear. Understanding cellular internalization facilitate development gene vectors. In present study, we evaluated process a previously designed CPP, STR-KV, complexed with small interference RNA (siRNA) targeting at glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Using heparin treatment chemical endocytic inhibitors, elucidated that electrostatic interaction STR-KV/siRNA complex sulfate proteoglycans cell membrane surface triggered energy-independent majority complexes, which most likely through direct translocation pathway. The intracellular trafficking kinetics observed by confocal microscopy also confirmed was uptaken nonendocytic