Real-time in vivo quantitative monitoring of drug release by dual-mode magnetic resonance and upconverted luminescence imaging

Insufficient or excess drug doses, due to unknown actual drug concentrations at the focus, are one of the main causes of chemotherapy failure for cancers. In this regard, the real-time monitoring of the release of anticancer drugs from nanoparticle drug delivery systems is of crucial importance, but it remains a critical and unsolved challenge. Herein, we report the proposal and development of a novel concept of real-time monitoring of NIR-triggered drug release in vitro and in vivo by using simultaneous upconverted luminescence (UCL) and magnetic resonance (MR) imaging. Such a monitoring strategy features the high sensitivity of UCL and the high-resolution, noninvasiveness, and tissue-depth-independence of MR imaging. The dual-mode real-time and quantitative monitoring of drug release can be applied to determine online the drug concentrations in vivo in the tissue regions of interest and, therefore, to avoid insufficient or excess drug dosings. Lighting up drug delivery: Multifunctional Gd core/hollow mesoporous silica shell nanoparticles were synthesized. With doxorubicin (DOX) fully loaded inside the nanoparticles, the upconverted luminescence (UCL) signals are quenched through luminescence resonance energy transfer (LRET), and the longitudinal relaxation time magnetic resonance (T₁-MR) signals are almost undetectable. Upon drug release, both the UCL and T₁-MR signals are restored. As a result, drug release can be detected by the designed dual-mode nanosensor (see figure; R₁: longitudinal relaxivity).