Increased Nanoparticle Delivery to Brain Tumors by Autocatalytic Priming for Improved Treatment and Imaging

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• 作者：Liang Han ; Derek K. Kong ; Ming-qiang Zheng ; Sasidhar Murikinati ; Chao Ma ; Peng Yuan ; Liyuan Li ; Daofeng Tian ; Qiang Cai ; Chunlin Ye ; Daniel Holden ; June-Hee Park ; Xiaobin Gao ; Jean-Leon Thomas ; Jaime Grutzendler ; Richard E. Carson ; Yiyun Huang ; Joseph M. Piepmeier ; Jiangbing Zhou
• 刊名：ACS Nano
• 出版年：2016
• 出版时间：April 26, 2016
• 年：2016
• 卷：10
• 期：4
• 页码：4209-4218
• 全文大小：578K
• 年卷期：0
• ISSN：1936-086X

文摘

The blood–brain barrier (BBB) is partially disrupted in brain tumors. Despite the gaps in the BBB, there is an inadequate amount of pharmacological agents delivered into the brain. Thus, the low delivery efficiency renders many of these agents ineffective in treating brain cancer. In this report, we proposed an “autocatalytic” approach for increasing the transport of nanoparticles into the brain. In this strategy, a small number of nanoparticles enter into the brain via transcytosis or through the BBB gaps. After penetrating the BBB, the nanoparticles release BBB modulators, which enables more nanoparticles to be transported, creating a positive feedback loop for increased delivery. Specifically, we demonstrated that these autocatalytic brain tumor-targeting poly(amine-co-ester) terpolymer nanoparticles (ABTT NPs) can readily cross the BBB and preferentially accumulate in brain tumors at a concentration of 4.3- and 94.0-fold greater than that in the liver and in brain regions without tumors, respectively. We further demonstrated that ABTT NPs were capable of mediating brain cancer gene therapy and chemotherapy. Our results suggest ABTT NPs can prime the brain to increase the systemic delivery of therapeutics for treating brain malignancies.