Key Laboratory on Luminescent and Real-Time Analytic Chemistry, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China.
Southwest University Hospital, Beibei, Chongqing, 400715, PR China.
Colloids Surf B Biointerfaces. 2017 Dec 1;160:207-214. doi: 10.1016/j.colsurfb.2017.09.034. Epub 2017 Sep 14.
A novel targeting drug delivery system for cancer therapy based on H-triggered bubble-generating nanosystems (BGNSs) was engineered. First, hollow mesoporous silica nanoparticles (HMSNs) were used to load doxorubicin (DOX). Then, the obtained drug-loaded HMSNs were treated with NaHCO to prepare the BGNSs. The BGNSs were coated with polydopamine (pDA), and finally, folic acids (FA) were anchored on the nanosystems to obtain the desired nanoscale drug delivery system (BGNSs@pDA-FA). BGNSs@pDA-FA was effectively internalized by cancer cells through folate receptor-mediated endocytosis and generated CO bubbles under the acidic environment of the lysosomes, thus enhancing lysosomal membrane permeability (LMP) to release caspase-3 into the cytoplasm, resulting in cancer cell death via an apoptosis-like pathway. Notably, we demonstrated that the BGNSs@pDA-FA exhibited a significant simultaneous synergetic cytotoxicity against MCF-7 cells and remarkably overcame the multidrug resistance (MDR) of MCF-7/ADR cells. Moreover, compared to free DOX and a nanosystem without FA modification (BGNSs), the BGNSs@pDA-FA induced relatively minor side effects in the MCF-10A cells. Therefore, the results showed that BGNSs@pDA-FA, as a targeted drug delivery system, have a good probability of overcoming the MDR of tumor cells with minor side effects on normal cells.
一种基于 H 触发产生气泡纳米系统（BGNSs）的新型癌症治疗靶向药物输送系统被设计出来。首先，空心介孔硅纳米粒子（HMSNs）被用于装载阿霉素（DOX）。然后，用碳酸氢钠处理载药的 HMSNs 以制备 BGNSs。BGNSs 被聚多巴胺（pDA）包裹，最后，叶酸（FA）被锚定在纳米系统上以获得所需的纳米级药物输送系统（BGNSs@pDA-FA）。BGNSs@pDA-FA 通过叶酸受体介导的内吞作用被癌细胞有效内化，并在溶酶体的酸性环境下产生 CO 气泡，从而增强溶酶体膜通透性（LMP），将半胱天冬酶-3释放到细胞质中，通过类似凋亡的途径导致癌细胞死亡。值得注意的是，我们证明了 BGNSs@pDA-FA 对 MCF-7 细胞表现出显著的协同细胞毒性，并显著克服了 MCF-7/ADR 细胞的多药耐药性（MDR）。此外，与游离 DOX 和没有 FA 修饰的纳米系统（BGNSs）相比，BGNSs@pDA-FA 在 MCF-10A 细胞中引起的副作用相对较小。因此，结果表明，作为靶向药物输送系统的 BGNSs@pDA-FA 具有克服肿瘤细胞多药耐药性的良好潜力，对正常细胞的副作用较小。
