Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Xinong Road 22, Yangling, Shaanxi 712100, China.
State Key Laboratory of Fine Chemicals, School of Chemistry, Dalian University of Technology, No. 2 linggong Road, Ganjingzi District, Dalian 116023, China.
ACS Appl Mater Interfaces. 2020 Jun 3;12(22):24611-24622. doi: 10.1021/acsami.0c06117. Epub 2020 May 19.
Although differently shaped mesoporous silica is widely studied, the formation of width-consistent mesoporous silica nanorods (MSNRs) with a precisely controlled aspect ratio (AR: length/width) is challenging and has not been reported. Herein, width-consistent (100 nm) MSNRs with ARs of 2, 3, 4, 6, 8, and 10 were obtained by increasing the concentrations while maintaining the molar ratio of cetyltrimethylammonium bromide (CTAB) and tetraethyl orthosilicate (TEOS). The results demonstrated that the as-prepared MSNR with an AR of 6 (AR6) possesses high cellular-uptake efficiency and drug-loading capacity. Thus, AR6-based cancer-cell-targeting nanosystems were designed. These nanosystems encapsulated doxorubicin (DOX) into the porous channel of AR6, adsorbed glucose oxidase (GOx), and then formed a polydopamine (PDA) layer for Siramesine (Siram, a lysosome dysfunctional drug) adsorption and folic acid modification. In this design, the PDA shell could prevent the leakage of loading components and keep the activity of GOx during delivery while achieving an on-demand drug release in the targeted location and photothermal therapy under near-infrared irradiation. The increase in temperature was highly beneficial for elevating the catalytic efficiency of GOx, accelerating the consumption of intracellular glucose, and generating a relatively high level of cytotoxic HO, all of which enhanced starvation and oxidative therapies. Siram was employed to inhibit lysosomal metabolism and accompany GOx to reach a dual-enhanced starvation therapy effect. In addition, DOX entered the nucleus and altered DNA for chemotherapy. The results showed that the nanosystems have superior therapeutic efficacy against cancer cells and not much toxicity to normal cells. Therefore, this study provides a novel strategy for lysosome dysfunctional synergistic chemotherapy/photothermal therapy/starvation therapy/oxidative therapy based on MSNR.
尽管不同形状的介孔硅材料被广泛研究，但具有精确控制的纵横比（AR：长度/宽度）的宽度一致的介孔硅纳米棒（MSNR）的形成具有挑战性，并且尚未报道。在此，通过增加浓度同时保持十六烷基三甲基溴化铵（CTAB）和正硅酸乙酯（TEOS）的摩尔比，获得了具有 2、3、4、6、8 和 10 的 AR 的宽度一致（100nm）的 MSNR。结果表明，具有 AR 的 MSNR 具有高细胞摄取效率和载药能力。因此，设计了基于 AR 的癌细胞靶向纳米系统。这些纳米系统将阿霉素（DOX）封装到 AR6 的多孔通道中，吸附葡萄糖氧化酶（GOx），然后形成聚多巴胺（PDA）层，用于 Siramesine（一种溶酶体功能障碍药物）吸附和叶酸修饰。在该设计中，PDA 壳可以防止负载成分的泄漏，并在输送过程中保持 GOx 的活性，同时在靶向部位实现按需药物释放和近红外照射下的光热治疗。温度的升高非常有利于提高 GOx 的催化效率，加速细胞内葡萄糖的消耗，并产生相对较高水平的细胞毒性 HO，所有这些都增强了饥饿和氧化治疗。Siram 被用于抑制溶酶体代谢并伴随 GOx 达到双重增强的饥饿治疗效果。此外，DOX 进入细胞核并改变 DNA 进行化学治疗。结果表明，该纳米系统对癌细胞具有优异的治疗效果，对正常细胞的毒性不大。因此，本研究为基于 MSNR 的溶酶体功能障碍协同化学治疗/光热治疗/饥饿治疗/氧化治疗提供了一种新策略。
