Department of Dental Implant Center, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province , Anhui Medical University , Hefei 230032 , People's Republic of China.
Hangzhou Stomatological Hospital , University of Chinese Academy of Sciences , Hangzhou 310002 , People's Republic of China.
ACS Appl Mater Interfaces. 2018 Sep 19;10(37):31114-31123. doi: 10.1021/acsami.8b11408. Epub 2018 Sep 6.
Current magnetic resonance imaging (MRI)-guided pH-switching therapeutic platforms have encountered problems such as low relaxation rates, poor pH-switching efficiencies, and a lag in the drug release behind the MRI. Herein, we designed a nanoplatform with tunable pore size, which could match the size of drug molecules for pH-switching MRI and chemotherapy via ultrasmall manganese oxide-capped mesoporous silica nanoparticles (USMO@MSNs). USMO@MSN could quickly dissolve under weakly acidic conditions and leach abundant Mn ions (leaching ratio: 76%), enhancing the MR contrast. The longitudinal relaxation rate ( r) of USMO@MSNs significantly increased from 0.65 to 5.61 mM s as the pH decreased from 7.4 to 4.5, showing an ultrahigh-efficiency pH-switching T-weighted MR contrast ability for in vivo tumor. Meanwhile, the matching pore structure allowed effective loading of doxorubicin (DOX) on USMO@MSNs to form smart therapeutic system (USMO@MSNs-DOX). The DOX release rate was strongly proportional to the pH-switching MRI signal of USMO@MSNs-DOX, allowing the release of DOX to be efficiently monitored by MRI. Confocal observations indicated that USMO@MSNs-DOX could be effectively internalized by HSC3 cells, and the entire system showed a good pH-switching theranostic performance for HSC3 cells. Therefore, this simple pH-switching system provides a new avenue for timely cancer diagnosis and personalized therapy.
目前的磁共振成像（MRI）引导的 pH 转换治疗平台存在弛豫率低、pH 转换效率差以及药物释放滞后于 MRI 等问题。在此，我们设计了一种具有可调节孔径的纳米平台，该平台可以通过超小的氧化锰包覆介孔硅纳米粒子（USMO@MSNs）匹配药物分子的大小，实现 pH 转换 MRI 和化疗。USMO@MSN 在弱酸性条件下迅速溶解，并浸出丰富的 Mn 离子（浸出率：76%），增强磁共振对比。当 pH 从 7.4 降低到 4.5 时，USMO@MSNs 的纵向弛豫率（r）从 0.65 显著增加到 5.61mM s，表现出超高效率的 pH 转换 T 加权磁共振对比能力，可用于体内肿瘤。同时，匹配的孔结构允许阿霉素（DOX）有效负载于 USMO@MSNs 上，形成智能治疗系统（USMO@MSNs-DOX）。DOX 的释放率与 USMO@MSNs-DOX 的 pH 转换 MRI 信号呈强比例关系，允许通过 MRI 对 DOX 的释放进行有效监测。共聚焦观察表明，USMO@MSNs-DOX 可以被 HSC3 细胞有效内化，整个系统对 HSC3 细胞表现出良好的 pH 转换治疗性能。因此，这种简单的 pH 转换系统为癌症的及时诊断和个性化治疗提供了新途径。
