Combined Biomimetic MOF-RVG15 Nanoformulation Efficient Over BBB for Effective Anti-Glioblastoma in Mice Model

作者：Hao Wu, Yanhong Liu, Liqing Chen, Shuangqing Wang, Chao Liu, Heming Zhao, Mingji Jin, Shuang-Yan Chang, Xiuquan Quan, Minhu Cui, Hongshuang Wan, Zhonggao Gao, Wei Huang · 发表于：International Journal of Nanomedicine · 年份：2022 · DOI：10.2147/ijn.s387715 · 被引用次数：26 · 研究领域：Metal-Organic Frameworks: Synthesis and Applications、Nanoplatforms for cancer theranostics、Graphene and Nanomaterials Applications

Introduction: The blood–brain barrier (BBB) is a key obstacle to the delivery of drugs into the brain. Therefore, it is essential to develop an advanced drug delivery nanoplatform to solve this problem. We previously screened a small rabies virus glycoprotein 15 (RVG 15 ) peptide with 15 amino acids and observed that most of the RVG 15 -modified nanoparticles entered the brain within 1 h of administration. The high BBB penetrability gives RVG 15 great potential for brain-targeted drug delivery systems. Moreover, a multifunctional integrated nanoplatform with a high drug-loading capacity, tunable functionality, and controlled drug release is crucial for tumor treatment. Zeolitic imidazolate framework (ZIF-8) is a promising nanodrug delivery system. Methods: Inspired by the biomimetic concept, we designed RVG 15 -coated biomimetic ZIF-8 nanoparticles (RVG 15 [email protected] @ZIF-8) for docetaxel (DTX) delivery to achieve efficient glioblastoma elimination in mice. This bionic nanotherapeutic system was prepared by one-pot encapsulation, followed by coating with RVG 15 -PEG conjugates. The size, morphology, stability, drug-loading capacity, and release of RVG 15 [email protected] @ZIF-8 were thoroughly investigated. Additionally, we performed in vitro evaluation, cell uptake capacity, BBB penetration, and anti-migratory ability. We also conducted an in vivo evaluation of the biodistribution and anti-glioma efficacy of this bionic nanotherapeutic system in a mouse mode. Results...