Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China.
Int J Nanomedicine. 2020 Dec 17;15:10285-10304. doi: 10.2147/IJN.S283981. eCollection 2020.
Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations.
A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects.
The MSN@GO-HA was constructed by MSN (loading CA via physical diffusion) and GO-HA (modified with HA and loading DOX via π-π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively.
The MSN@GO-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSN@GO-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process.
The establishment of the MSN@GO-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.
联合化疗常受到化疗药物不同理化性质的影响，通过合理设计共载制剂可以改善这一情况。
设计了一种简单实用的氧化石墨烯（GO）包裹透明质酸（HA）修饰的介孔硅纳米粒子（MSN@GO-HA），用于同时递送肉桂醛（CA）和阿霉素（DOX），以增强它们对肿瘤细胞的联合治疗作用，并减少它们的应用缺陷。
通过静电吸附作用构建 MSN@GO-HA，其中 MSN 通过物理扩散装载 CA，GO-HA 通过π-π堆积作用装载 DOX 并修饰 HA。对其进行理化性质表征、血清稳定性和体外释放研究。检测对不同细胞的细胞毒性，随后进行肿瘤细胞摄取实验。还评估了 MCF-7 细胞中细胞内活性氧（ROS）变化、线粒体功能和 caspase-3/-9 活性。
MSN@GO-HA 纳米粒子在 FBS 溶液中稳定，并表现出 pH 响应性释放行为，有利于增加 CA 和 DOX 在肿瘤细胞中的积累，从而增强治疗效果。MSN@GO-HA 对 MCF-7 人乳腺癌细胞的细胞毒性高于 H9c2 心肌细胞，这不仅归因于 HA 对肿瘤细胞的主动靶向作用，还与 CA 诱导 MCF-7 细胞内固有凋亡途径的激活有关，这与 CA 特异性 ROS 信号放大和干扰线粒体功能有关。此外，上述过程还增强了 DOX 的疗效。
MSN@GO-HA 纳米粒子的建立在促进 CA 和 DOX 的优势和限制其劣势方面发挥了作用，从而发挥了它们的功能，实现了高效的癌症治疗。
