Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
Hubei Province Clinical Research Center for Precision Medicine for Critical Illness, Wuhan, P. R. China.
J Microencapsul. 2022 Jan;39(1):25-36. doi: 10.1080/02652048.2021.2014586. Epub 2021 Dec 20.
To prepare the hyaluronic acid-coated Olaparib-loaded PEI - PLGA nanoparticles (HA-Ola-PPNPs) and investigate their tumour-targeted anticancer effect.
The synthesis of HA-Ola-PPNPs was verified by DLS, TEM and SEM, followed was measured its cytotoxicity using CCK-8 assay. Confocal microscopy was used to observe the cellular uptake. Cell apoptosis was analysed by flow cytometry, biological SEM, and TEM. The expression of related proteins within the tumour site was investigated by immunostaining.
The prepared HA-Ola-PPNPs showed a diameter of ∼160 nm with a negatively charged surface (-16.9 ± 2.7 mV) and sustained drug release behaviour. And the encapsulation efficiency of HA-Ola-PPNPs was 78.63 ± 5.29%. HA-Ola-PPNPs exhibited efficient and antitumor activities. HA-Ola-PPNPs induced cell apoptosis by upregulating Bax, Cytochrome C, and Caspase 3, downregulating Bcl-2 in breast cancer-bearing mice.
According to the results, the Ola-loaded and HA-coated PEI - PLGA nanoparticles could be considered as a powerful tumour-targeted drug delivery system for TNBC treatment.
制备透明质酸（HA）包裹奥拉帕利（Ola）载多聚赖氨酸-聚乳酸-羟基乙酸共聚物（PEI-PLGA）纳米粒（HA-Ola-PPNPs），并研究其肿瘤靶向抗癌作用。
通过动态光散射（DLS）、透射电子显微镜（TEM）和扫描电子显微镜（SEM）验证 HA-Ola-PPNPs 的合成，然后使用 CCK-8 法测定其细胞毒性。通过共聚焦显微镜观察细胞摄取。通过流式细胞术、生物扫描电子显微镜（SEM）和透射电子显微镜（TEM）分析细胞凋亡。通过免疫染色法研究肿瘤部位相关蛋白的表达。
所制备的 HA-Ola-PPNPs 粒径约为 160nm，表面带负电荷（-16.9±2.7mV），具有持续的药物释放行为。HA-Ola-PPNPs 的包封效率为 78.63±5.29%。HA-Ola-PPNPs 表现出高效和抗肿瘤活性。HA-Ola-PPNPs 通过上调乳腺癌荷瘤小鼠中的 Bax、细胞色素 C 和 Caspase 3，下调 Bcl-2 诱导细胞凋亡。
根据结果，负载奥拉帕利和包裹透明质酸的多聚赖氨酸-聚乳酸-羟基乙酸共聚物纳米粒可以被认为是治疗三阴性乳腺癌的一种强大的肿瘤靶向药物递送系统。
