期刊
ACS APPLIED MATERIALS & INTERFACES
卷 7, 期 38, 页码 21442-21454出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b06429
关键词
TR peptide; BBB penetrating; glioma targeting; cancer stem cells; VM channels
资金
- National Basic Research Program of China (973 Program) [2013CB932504]
- National Natural Science Foundation of China [81373337]
- Sichuan Province Infrastructure Platform of Science and Technology [15010116]
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 brain 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 alpha(v)beta(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 alpha(v)beta(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.
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