Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha 410013, P. R. China
Department of Cardiology , the Second Hospital of Shandong University , Jinan 250000 , P. R. China.
ACS Appl Mater Interfaces. 2019 Aug 7;11(31):28254-28266. doi: 10.1021/acsami.9b04735. Epub 2019 Jul 23.
Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.
栀子苷（HED）的抗癌活性较差，其作用机制尚不清楚且不系统。用于癌症治疗的游离药物存在靶向性和疗效差等缺点。为了解决这个问题，我们构建了一种由黑磷量子点（BPQDs）组成的纳米平台，其表面被血小板膜（PLTm）伪装，载有 HED，称为 PLT@BPQDs-HED。PLTm 囊泡作为外壳，可以包裹多个高效载药的纳米核，从而靶向肿瘤部位，并显著提高抗肿瘤活性。与游离 HED 相比，该平台显著降低了肿瘤细胞的活力和线粒体膜电位（MMP），同时增加了细胞内活性氧（ROS）的产生。该平台还显著增加了末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）阳性细胞的数量，并减少了 Ki-67 阳性细胞的数量。此外，该平台上调促凋亡因子 Bax，下调抗凋亡分子 Bcl-2，激活 Caspase-9 和 Caspase-3，并刺激细胞色素 C 释放。此外，该平台促进自噬体的形成，上调 Beclin-1，并促进 LC3-I 向 LC3-II 的转化。本研究表明，上述平台显著增强了肿瘤的靶向性，并促进了肿瘤细胞中线粒体介导的细胞凋亡和自噬。
