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Distinct transduction modes of arginine-rich cell-penetrating peptides for cargo delivery into tumor cells
作者:Ma DX, Shi NQ(co-first author), Qi XR.
關鍵字:Cell-penetrating peptides,Endocytosis,Heparan sulfate proteoglycans,Macropinocytosis, Nona-arginine
論文來源:期刊
具體來源:International Journal of Pharmaceutics, 2011,419(1-2):200-208.(SCI,IF=3.994)
發表時間:2011年

The application of cell-penetrating peptides (CPPs) for delivering various cargo molecules with biological functions into cells has gained much attention in recent years. However, the internalization mechanisms and delivery properties of CPP–cargo remains controversial. In this study, low- and highmolecular-weight cargoes attached to arginine-rich CPPs were employed: the former was the fluorescein isothiocyanate-labeled nona-arginine (CPP–FITC), and the latter was the fluorescently labeled nonaarginine–avidin complex (CPP–avidin). We measured the intracellular trafficking of CPP–FITC and CPP–avidin in four cancer cell lines in a series of microenvironments altered by the presence or absence of serum, different temperatures and different incubation times. The results revealed that CPP–cargo delivery exhibited no specificity toward any cell line, but the levels were found to be related to cell

type and cargo. Furthermore, their endocytic mechanisms were investigated via incubation with related endocytic inhibitors. Two different types of CPP–cargo were required to cross the plasma membrane to bind to cell surface-associated heparan sulfate proteoglycans in a time-dependent manner. CPPs and small cargoes attached to CPP may enter cells rapidly via direct translocation in addition to the endocytic route. Translocation of large components linked to CPP tended to be mediated by macropinocytosis in an energy-dependent manner with slower rates for larger compounds. In contrast, the clathrin-dependent pathway is not essential to the translocation of either type of CPP–cargo.




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