Tianjin Nano-Biotechnology and Translational Medicine Lab School of Materials Science and Engineering, Tianjin University, Tianjin, 300350, China.
School of Environmental and Chemical Engineering, Jiangsu Ocean University, Lianyungang, 222005, China.
Macromol Biosci. 2021 Apr;21(4):e2000392. doi: 10.1002/mabi.202000392. Epub 2021 Jan 27.
The excellent biocompatibility drug delivery system for effective treatment of glioma is still greatly challenged by the existence of blood-brain barrier, blood-brain tumor barrier, and the tissue toxicity caused by chemotherapy drugs. In this study, poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) is used for the first time for modifying third-generation poly(amidoamine) (PAMAM) to enhance their brain tumor-targeted drug delivery ability as well as simultaneously reducing the toxicity of PAMAM dendrimers and the tissue toxicity of the loaded doxorubicin (DOX). The cytotoxicity, the therapeutic ability in vitro, and the brain tumor-targeted ability of the PMPC modified PAMAM nanoparticles are further studied. Results indicate that PMPC, as a dual-functional modifier, can significantly reduce the cytotoxicity of PAMAM dendrimers, while efficiently target the brain tumor. In addition, the therapeutic effect of DOX-loaded PAMAM-PMPC in mice inoculated with U-87 is also studied in vivo. In comparison with DOX solution, DOX-loaded PAMAM-PMPC alleviates weight loss of tumor-inoculated mice and reduces the cardiotoxicity of DOX. The tumor growth inhibition, in vivo, is significantly increased up to (80.76 ± 1.66)%. In conclusion, this strategy of PMPC dual-functional targeted nanocarrier provides a new method for the delivery of chemotherapeutic drugs to treat glioma.
用于有效治疗神经胶质瘤的优异生物相容性药物输送系统仍然受到血脑屏障、血脑肿瘤屏障以及化疗药物引起的组织毒性的极大挑战。在本研究中，首次使用聚（2-甲基丙烯酰氧乙基磷酰胆碱）（PMPC）修饰第三代聚（酰胺-胺）（PAMAM），以增强其脑肿瘤靶向药物输送能力，同时降低 PAMAM 树枝状大分子的毒性和载阿霉素（DOX）的组织毒性。进一步研究了 PMPC 修饰的 PAMAM 纳米粒的细胞毒性、体外治疗能力和脑肿瘤靶向能力。结果表明，PMPC 作为双功能修饰剂，可显著降低 PAMAM 树枝状大分子的细胞毒性，同时有效靶向脑肿瘤。此外，还在接种 U-87 的小鼠体内研究了载 DOX 的 PAMAM-PMPC 的治疗效果。与 DOX 溶液相比，载 DOX 的 PAMAM-PMPC 减轻了荷瘤小鼠的体重减轻，并降低了 DOX 的心脏毒性。体内肿瘤生长抑制率显著提高至（80.76±1.66）%。总之，这种 PMPC 双功能靶向纳米载体的策略为治疗神经胶质瘤的化疗药物输送提供了一种新方法。
