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Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple Barriers
journal contribution
posted on 2017-05-12, 00:00 authored by Huitong Ruan, Xishan Chen, Cao Xie, Beibei Li, Man Ying, Yu Liu, Mingfei Zhang, Xuesai Zhang, Changyou Zhan, Wuyuan Lu, Weiyue LuMalignant glioma,
the most frequent and aggressive central nervous system (CNS) tumor,
severely threatens human health. One reason for its poor prognosis
and short survival is the presence of the blood–brain barrier
(BBB) and blood–brain tumor barrier (BBTB), which restrict
the penetration of therapeutics into the brain at different stages
of glioma. Herein, inspired by the peptide stapling technique, we
designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled
RGD, sRGD) to facilitate BBB penetration while retaining the capacity
of BBTB penetration and targeting ability to glioma cells. As expected,
sRGD-modified micelles were able to penetrate the in vitro BBB model
while retaining the glioma targeted capability. The results of the
in vivo imaging studies further revealed that this nanocarrier could
not only efficiently transverse the intact BBB of normal mice, but
also could specifically target glioma cells of intracranial glioma-bearing
nude mice. Furthermore, Paclitaxel-loaded sRGD-modified micelles exhibited
improved antiglioma efficacy in vitro and significantly prolonged
survival time of glioma-bearing nude mice. Overall, this sRGD peptide
showed potency for glioma-targeted drug delivery by overcoming multiple
barriers.
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glioma-targeted drug deliveryBBTBStapled RGD Peptide Enables Glioma-Targeted Drug Deliveryglioma cellsCNSbarriersurvivalBBBpenetrationvivo imaging studiesglioma-bearingOvercoming Multiple Barriers Malignant gliomatumorPaclitaxel-loaded sRGD-modified micellespeptide stapling techniquecyclic RGD ligand