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Effective pH-Activated Theranostic Platform for Synchronous Magnetic Resonance Imaging Diagnosis and Chemotherapy.

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 Mn2+ ions (leaching ratio: 76%), enhancing the MR contrast. The longitudinal relaxation rate ( r1) of USMO@MSNs significantly increased from 0.65 to 5.61 mM-1 s-1 as the pH decreased from 7.4 to 4.5, showing an ultrahigh-efficiency pH-switching T1-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.