State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Small. 2020 Feb;16(8):e1906985. doi: 10.1002/smll.201906985. Epub 2020 Jan 31.
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 MnO nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo-Tf to obtain MnO @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.
血脑屏障（BBB）是改善胶质母细胞瘤诊断和治疗临床效果的最大障碍。因此，开发一种能够高效穿透血脑屏障并实现精确诊断和治疗的新型纳米平台非常重要。在此，通过一种改良的温和生物矿化过程，构建了一种基于全转铁蛋白（holo-Tf）的智能纳米平台，其原位生长 MnO 纳米晶体。此外，原卟啉（ppIX）作为声敏剂被共轭到 holo-Tf 上，得到 MnO@Tf-ppIX 纳米颗粒（TMP）。由于在制备过程中 holo-Tf 的功能遗传，TMP 可以有效地穿透血脑屏障，对原位胶质母细胞瘤进行高度特异性磁共振（MR）成像。通过声动力学治疗，在 C6 肿瘤异种移植模型中实现了对肿瘤生长的明显抑制。重要的是，实验还表明 TMP 纳米平台具有良好的生物相容性和生物安全性，有利于潜在的临床转化。
