a School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University , Wenzhou , China.
b School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University , Guangzhou , China.
Drug Deliv. 2019 Dec;26(1):732-743. doi: 10.1080/10717544.2019.1642419.
Multifunctional core-shell nanocarriers based on zinc oxide (ZnO)-gated magnetic mesoporous silica nanoparticles (MMSN) were prepared for cancer treatment through magnetic targeting and pH-triggered controlled drug release. Under an external magnetic field, the MMSN could actively deliver chemotherapeutic agent, daunomycin (DNM), to the targeted sites. At neutral aqueous, the functionalized MMSN could stably accommodate the DNM molecules since the mesopores were capped by the ZnO gatekeepers. In contrast, at the acid intercellular environment, the gatekeepers would be removed to control the release of drugs due to the dissolution of ZnO. Meanwhile, ZnO quantum dots not only rapidly dissolve in an acidic condition of cancer cells but also enhance the anti-cancer effect of Zn. An controlled release proliferation indicated that the acid sensitive ZnO gatekeepers showed well response by the 'on-off' switch of the pores. Cellular experiments against cervical cancer cell (HeLa cells) further showed that functionalized MMSN significantly suppressed cancer cells growth through synergistic effects between the chemotherapy and Zn ions with monitoring the treatment process. These results suggested that the ZnO-gated MMSN platform is a promising approach to serve as a pH-sensitive system for chemotherapies delivery and Zn controlled release for further application in the treatment of various cancers by synergistic effects.
基于氧化锌(ZnO)门控磁性介孔硅纳米粒子(MMSN)的多功能核壳纳米载体通过磁靶向和 pH 触发的控制药物释放用于癌症治疗。在外磁场作用下,MMSN 可以主动将化疗药物阿霉素(DNM)递送到靶向部位。在中性水相中,由于介孔被 ZnO 门控剂封闭,功能化的 MMSN 可以稳定地容纳 DNM 分子。相比之下,在细胞内酸性环境中,由于 ZnO 的溶解,门控剂会被除去以控制药物的释放。同时,ZnO 量子点不仅在癌细胞的酸性条件下迅速溶解,而且还增强了 Zn 的抗癌效果。一种控制释放增殖实验表明,酸敏感的 ZnO 门控剂通过孔的“开-关”开关表现出良好的响应。针对宫颈癌细胞(HeLa 细胞)的细胞实验进一步表明,功能化 MMSN 通过化疗和 Zn 离子的协同作用显著抑制癌细胞生长,并监测治疗过程。这些结果表明,ZnO 门控 MMSN 平台是一种有前途的方法,可以作为一种 pH 敏感的化疗药物输送和 Zn 控制释放系统,用于通过协同作用进一步治疗各种癌症。