Multifunctional Micelles Containing pH-sensitive Bonds and PEGylated TAT Peptide for Enhanced In- Vitro Cellular Internalization

摘要

New developments with pH-sensitive long-circulating PEG-phosphatidylethanolamine (PEG-PE)-based micelles, modified with cell-penetrating TAT peptide (TATp) moieties are described. By using TATp, conjugated with a short PEG-PE spacer, and a degradable pH-sensitive hydrazone bond between long PEG spacer and PE (PEG-Hz-PE), we have produced a multifunctional carrier with a "shielded" surface-attached TATp at normal pH which is exposed following the degradation of the hydrazone bond at lowered pH and have studied its interaction with cells. Higher uptake of TATp-containing micelles and enhanced micelles-cell interaction at lower pH in vitro was observed indicating TATp de-shielding compared to pH at 7.4. In addition, at lower pH, increased cytotoxicity was observed when the anticancer drug paclitaxel was encapsulated into the modified micelles.