Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Green Preparation and Application of Functional Materials of Ministry of Education, Hubei University, Wuhan, Hubei 430062, PR China.
Glyn O. Philips Hydrocolloid Research Centre at HUT, Hubei University of Technology, Wuhan, Hubei 430068, PR China.
Colloids Surf B Biointerfaces. 2018 Jul 1;167:407-414. doi: 10.1016/j.colsurfb.2018.04.038. Epub 2018 Apr 21.
Due to the difference of pH values between normal tissues, tumor tissues and intracellular environments, DOX@MSN-CD-PEG, a stepwise-acid-active organic/inorganic hybrid drug delivery system (DDS) was reported in this article. The inorganic mesoporous silica nanoparticle (MSN) was introduced for loading of doxorubicin hydrochloride (DOX). Then organic components were applied to achieve the stepwise-acid-active intracellular drug release: MSN was capped with a β-cyclodextrine (β-CD) based host-guest system via pH-sensitive epoxy bond. Then PEG was grafted outside of the carriers through pH-sensitive benzoic imine bond. With the protection of PEG layer, the carriers were difficult cellular uptake by normal cells but could be "acid-activated" for cytophagy by cancer cells in the slightly acidic environments in tumor tissues because of the abscission of PEG. Inside the cells, the more acidic environments could further "activate" the carriers to release DOX as the leaving of the host-guest system. The fabrication processes of DOX@MSN-CD-PEG were monitored. And the stepwise-acid-active property of which was investigated by acid-triggered PEG abscission studies and in vitro drug release studies at pH 7.4 and 6.5, respectively. The in vitro cellular cytotoxicity and cellular uptake behavior were also investigated. In summary, the stepwise-acid-active hybrid DDS should be considerable for cancer therapy.
由于正常组织、肿瘤组织和细胞内环境之间 pH 值的差异，本文报道了一种逐步酸激活的有机/无机杂化药物传递系统（DDS）DOX@MSN-CD-PEG。引入了无机介孔硅纳米颗粒（MSN）来负载盐酸多柔比星（DOX）。然后应用有机成分实现逐步酸激活的细胞内药物释放：MSN 通过 pH 敏感的环氧键与基于β-环糊精（β-CD）的主客体系统封闭。然后通过 pH 敏感的苯甲酰亚胺键将 PEG 接枝在载体的外部。由于 PEG 层的保护，载体很难被正常细胞摄取，但可以在肿瘤组织中稍酸性环境中的癌细胞中被“酸激活”进行细胞吞噬，因为 PEG 的脱落。在细胞内，更酸性的环境可以进一步“激活”载体以释放 DOX，因为主客体系统的离去。监测了 DOX@MSN-CD-PEG 的制备过程。通过酸触发 PEG 脱落研究和分别在 pH 值为 7.4 和 6.5 时的体外药物释放研究，研究了其逐步酸激活特性。还研究了体外细胞毒性和细胞摄取行为。总之，这种逐步酸激活的杂化 DDS 应该对癌症治疗有很大的意义。
