d-Retroenantiomer of Quorum-Sensing Peptide-Modified Polymeric Micelles for Brain Tumor-Targeted Drug Delivery.

Compared to that of other tumors, various barriers, such as the blood-brain barrier (BBB), enzymatic barriers, and the blood-brain tumor barrier, severely impede the successful treatment of gliomas. Peptide ligands were frequently used as targeting moieties to mediate brain tumor-targeted drug delivery. WSW (SYPGWSW) is a recently reported quorum-sensing (QS) peptide that is able to efficiently cross the BBB. Even though linear WSW traverses the BBB in vitro, its in vivo targeting ability has been greatly impaired due to proteolysis. Here, we developed a stable peptide, WSW (WSWGPYS), using the retro-inverso isomerization technique to achieve an enhanced antiglioma effect. In vitro studies have demonstrated that both the WSW and WSW peptides possessed excellent tumor-homing properties and barrier-penetration abilities, whereas WSW exhibited exceptional stability in serum and maintained its targeting ability after serum preincubation. In vivo, WSW-modified probes and micelles accumulated more efficiently in the glioma region in comparison with WSW-modified probes and micelles because of full resistance to proteolysis in blood circulation. As expected, WSW-modified paclitaxel (PTX)-loaded micelles (WSW Micelle/PTX) exhibited the longest median survival time among glioma-bearing nude mice. Our results suggested that the QS peptide appears to be a promising targeting moiety, with potential applications in glioma-targeted drug delivery.