Yan Jiaqi, Xu Xiaoyu, Zhou Junnian, Liu Chang, Zhang Lirong, Wang Dongqing, Yang Fan, Zhang Hongbo
The Center for Drug Research and Development and Engineering & Technology Research Center for Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong China.
Pharmaceutical Sciences Laboratory and Turku Bioscience Center, Åbo Akademi University, FI-20520 Turku, Finland.
ACS Appl Bio Mater. 2020 Feb 17;3(2):1216-1225. doi: 10.1021/acsabm.9b01111. Epub 2020 Jan 27.
A pH/redox-triggered mesoporous silica nanoparticle (MSN)-based nanoplatform has been fabricated for doxorubicin/paclitaxel (DOX/PTX) codelivery. In this drug-delivery system (DDS), PTX is covalently attached to the surface of DOX loaded MSN via a linker with disulfide bond. By directly attaching PTX to MSN, we can significantly enhance the PTX́s loading degree and achieve the optimum drug loading ratio to DOX, therefore, to generate the best synergistical effect. More importantly, PTX and the linker act as a redox-sensitive "gate" to precisely control the release profile of DOX and PTX. Subsequently, polystyrenesulfonate (PSS) is electrostatically coated to DOX loaded MSN-PTX in microfluidics to achieve acidic pH responsive, because the free amino group on MSN surface has a protonation state at acidic pH, and the electrostatic interaction will be destroyed at pH 5. In addition, PSS can also neutralize the surface zeta potential, thus reduce the nonspecific endocytosis of healthy cells. By evaluating cell viability in cancer cell BT549 and healthy breast cell MCF-10A, we observed that the nanoparticles can selectively release DOX and PTX and eliminate cancer cells, while they will have negligible effect on the healthy breast cells, due to the acidic and redox microenvironment in cancer cells. Overall, we have developed a nanoplatform for precise DOX/PTX combination therapy with high selectivity between cancer cells and healthy cells.
一种基于pH/氧化还原触发的介孔二氧化硅纳米颗粒（MSN）的纳米平台已被制备用于阿霉素/紫杉醇（DOX/PTX）的共递送。在这个药物递送系统（DDS）中，PTX通过一个带有二硫键的连接子共价连接到负载DOX的MSN表面。通过直接将PTX连接到MSN上，我们可以显著提高PTX的负载量，并实现与DOX的最佳药物负载比例，从而产生最佳的协同效应。更重要的是，PTX和连接子充当氧化还原敏感的“门”，以精确控制DOX和PTX的释放曲线。随后，在微流控中通过静电作用将聚苯乙烯磺酸盐（PSS）包覆到负载DOX的MSN-PTX上，以实现酸性pH响应，因为MSN表面的游离氨基在酸性pH下具有质子化状态，并且在pH 5时静电相互作用将被破坏。此外，PSS还可以中和表面zeta电位，从而减少健康细胞的非特异性内吞作用。通过评估癌细胞BT549和健康乳腺细胞MCF-10A中的细胞活力，我们观察到纳米颗粒可以选择性地释放DOX和PTX并消除癌细胞，而由于癌细胞中的酸性和氧化还原微环境，它们对健康乳腺细胞的影响可忽略不计。总体而言，我们开发了一种纳米平台，用于在癌细胞和健康细胞之间具有高选择性的精确DOX/PTX联合治疗。
