Liposomes Combined an Integrin 伪v尾3-Specific Vector with pH-Responsible Cell-Penetrating Property for Highly Effective Antiglioma Therapy through the Blood鈥揃rain Barrier

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• 作者：Kairong Shi ; Yang Long ; Chaoqun Xu ; Yang Wang ; Yue Qiu ; Qianwen Yu ; Yayuan Liu ; Qianyu Zhang ; Huile Gao ; Zhirong Zhang ; Qin He
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：September 30, 2015
• 年：2015
• 卷：7
• 期：38
• 页码：21442-21454
• 全文大小：1112K
• ISSN：1944-8252

文摘

Glioma, one of the most common aggressive malignancies, has the highest mortality in the present world. Delivery of nanocarriers from the systemic circulation to the glioma sites would encounter multiple physiological and biological barriers, such as blood鈥揵rain barrier (BBB) and the poor penetration of nanocarriers into the tumor. To circumvent these hurdles, the paclitaxel-loaded liposomes were developed by conjugating with a TR peptide (PTX-TR-Lip), integrin 伪_v尾₃-specific vector with pH-responsible cell-penetrating property, for transporting drug across the BBB and then delivering into glioma. Surface plasmon resonance (SPR) studies confirmed the very high affinity of TR-Lip and integrin 伪_v尾₃. In vitro results showed that TR-Lip exhibited strong transport ability across BBB, killed glioma cells and brain cancer stem cells (CSCs), and destroyed the vasculogenic mimicry (VM) channels. In vivo results demonstrated that TR-Lip could better target glioma, and eliminated brain CSCs and the VM channels in tumor tissues. The median survival time of tumor-bearing mice after administering PTX-TR-Lip (45 days) was significantly longer than that after giving free PTX (25.5 days, p < 0.001) or other controls. In conclusion, PTX-TR-Lip would improve the therapeutic efficacy of brain glioma in vitro and in vivo.