Key Laboratory of Marine Drugs, Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266237, China.
Biomacromolecules. 2021 Jul 12;22(7):2921-2934. doi: 10.1021/acs.biomac.1c00314. Epub 2021 Jun 28.
Glioblastoma (GBM) is a fatal brain tumor with poor prognosis. Blood-brain barrier (BBB) prevents the effective delivery of chemotherapeutic agents to GBM. Herein, we developed a pH/reduction-sensitive carboxymethyl chitosan nanogel (CMCSN) modified by targeting peptide angiopep-2 (ANG) and loaded with doxorubicin (DOX). The multifunctional nanogel (DOX-ANG-CMCSN) exhibited good pH and reduction sensitivity, ideal stability, and biocompatibility. Its hydrodynamic diameter was 190 nm, drug loading was 12.7%, and the cumulative release rate of 24 h was 82.3% under the simulated tumor microenvironment. More importantly, the modification of ANG significantly enhanced BBB penetration and tumor targeting ability both and . DOX-ANG-CMCSN achieved 2-3-fold higher uptake and an enhanced antitumor activity compared with nontargeted DOX-CMCSN. Therefore, the targeted nanogels with the pH/reduction dual-stimuli response may provide a promising platform for GBM-targeted chemotherapy.
胶质母细胞瘤（GBM）是一种预后不良的致命脑肿瘤。血脑屏障（BBB）阻止化疗药物有效递送至 GBM。在此，我们开发了一种由靶向肽血管生成素-2（ANG）修饰并负载多柔比星（DOX）的 pH/还原敏感羧甲基壳聚糖纳米凝胶（CMCSN）。多功能纳米凝胶（DOX-ANG-CMCSN）表现出良好的 pH 和还原敏感性、理想的稳定性和生物相容性。其水动力学直径为 190nm，药物载药量为 12.7%，在模拟肿瘤微环境下 24 小时的累积释放率为 82.3%。更重要的是，ANG 的修饰显著增强了 BBB 穿透和肿瘤靶向能力。与非靶向 DOX-CMCSN 相比，DOX-ANG-CMCSN 的摄取量增加了 2-3 倍，抗肿瘤活性增强。因此，具有 pH/还原双重刺激响应的靶向纳米凝胶可为 GBM 靶向化疗提供有前途的平台。
