Intelligent Nanocomposites with Intrinsic Blood-Brain-Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma
Intelligent Nanocomposites with Intrinsic Blood-Brain-Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma
复制标题
具有内在血脑屏障穿越能力的智能纳米复合材料，专为胶质母细胞瘤的高度特异性磁共振成像和声动力治疗而设计
DOI：
10.1002/smll.201906985
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发表时间：
2020-01-31
期刊：
影响因子：
13.3
通讯作者：
Wang, Han
中科院分区：
文献类型：
--
作者：
Liang, Kaicheng;Li, Zhicong;Wang, Han
血脑屏障（blood-brain barrier，BBB）是影响胶质母细胞瘤临床诊断和治疗效果的重要障碍。因此，开发一种能够有效穿过血脑屏障并实现精确诊断和治疗的新型纳米平台具有重要意义。本文通过温和的生物矿化过程构建了一种基于全转铁蛋白（holo-Tf）的智能纳米平台，并原位生长了MnO 2纳米晶。此外，原卟啉（ppIX），作为声敏剂，然后共轭到holo-Tf，以获得MnO 2 @Tf-ppIX纳米粒子（TMP）。由于在制造过程中holo-Tf的功能遗传，TMP可以有效地穿过BBB，用于原位胶质母细胞瘤的高度特异性磁共振（MR）成像。在C6肿瘤异种移植模型中，通过声动力疗法实现了对肿瘤生长的明显抑制。重要的是，实验还表明TMP纳米平台具有令人满意的生物相容性和生物安全性，这有利于潜在的临床转化。
The blood-brain barrier (BBB) is the most important obstacle to improving the clinical outcomes of diagnosis and therapy of glioblastoma. Thus, the development of a novel nanoplatform that can efficiently traverse the BBB and achieve both precise diagnosis and therapy is of great importance. Herein, an intelligent nanoplatform based on holo-transferrin (holo-Tf) with in situ growth of MnO2 nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo-Tf to obtain MnO2@Tf-ppIX nanoparticles (TMP). Because of the functional inheritance of holo-Tf during fabrication, TMP can effectively traverse the BBB for highly specific magnetic resonance (MR) imaging of orthotopic glioblastoma. Clear suppression of tumor growth in a C6 tumor xenograft model is achieved via sonodynamic therapy. Importantly, the experiments also indicate that the TMP nanoplatform has satisfactory biocompatibility and biosafety, which favors potential clinical translation.