Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple Barriers
Stapled RGD Peptide Enables Glioma-Targeted Drug Delivery by Overcoming Multiple Barriers
复制标题
装订 RGD 肽通过克服多重障碍实现神经胶质瘤靶向药物输送
DOI：
10.1021/acsami.7b03682
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发表时间：
2017-05-31
影响因子：
9.5
通讯作者：
Lu, Weiyue
中科院分区：
文献类型：
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作者：
Ruan, Huitong;Chen, Xishan;Lu, Weiyue
恶性胶质瘤是中枢神经系统最常见、最具侵袭性的肿瘤，严重威胁着人类的健康。其预后差和生存期短的一个原因是血脑屏障（BBB）和血脑肿瘤屏障（BBTB）的存在，这限制了治疗剂在胶质瘤的不同阶段渗透到脑中。在本文中，受肽钉合技术的启发，我们设计了经由全烃钉合（钉合的RGD，sRGD）的环状RGD配体以促进BBB穿透，同时保留容量。BBTB对胶质瘤细胞的穿透和靶向能力。正如预期的那样，sRGD修饰的胶束能够穿透体外BBB模型，同时保留胶质瘤靶向能力。体内成像研究结果进一步表明，该纳米载体不仅能有效地穿过正常小鼠的完整血脑屏障，而且能特异性靶向颅内胶质瘤裸鼠的胶质瘤细胞。此外，紫杉醇负载sRGD修饰的胶束在体外表现出更好的抗胶质瘤效果，并显着延长荷胶质瘤裸鼠的生存时间。总的来说，这种sRGD肽通过克服多种障碍显示出用于神经胶质瘤靶向药物递送的效力。
Malignant 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 battier (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 efficientlytransverse 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.