Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education , Shanghai 201203, China.
Department of Pharmacology, School of Basic Medical Sciences, Fudan University , Shanghai 200032, China.
ACS Appl Mater Interfaces. 2017 Aug 9;9(31):25672-25682. doi: 10.1021/acsami.7b03518. Epub 2017 Jul 31.
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.
与其他肿瘤相比，各种障碍，如血脑屏障（BBB）、酶屏障和血脑肿瘤屏障，严重阻碍了胶质瘤的成功治疗。肽配体经常被用作靶向部分来介导脑肿瘤靶向药物传递。WSW（SYPGWSW）是一种最近报道的群体感应（QS）肽，能够有效地穿过 BBB。尽管线性 WSW 在体外穿过 BBB，但由于蛋白水解作用，其体内靶向能力大大受损。在这里，我们使用反式异构体异构化技术开发了一种稳定的肽 WSW（WSWGPYS），以实现增强的抗神经胶质瘤效果。体外研究表明，WSW 和 WSW 肽都具有出色的肿瘤归巢特性和穿透屏障的能力，而 WSW 在血清中表现出异常的稳定性，并且在血清孵育后保持其靶向能力。在体内，由于在血液循环中完全抵抗蛋白水解作用，WSW 修饰的探针和胶束在神经胶质瘤区域的积累效率更高。正如预期的那样，WSW 修饰的紫杉醇（PTX）载药胶束（WSW Micelle/PTX）在荷神经胶质瘤裸鼠中的中位生存时间最长。我们的结果表明，QS 肽似乎是一种有前途的靶向部分，具有在脑肿瘤靶向药物传递中的潜在应用。
