NIR-to-Red Upconversion Nanoparticles with Minimized Heating Effect for Synchronous Multidrug Resistance Tumor Imaging and Therapy.

Lanthanide-doped upconversion nanoparticles (UCNPs), especially the 808 nm activated UCNPs, are promising imaging agents for biological applications because of their minimal tissue overheating effects and low autofluorescence background. Optimizing the emission peaks located in the "biological window (600-1100 nm)" is of vital importance to obtain the maximum penetration depth and intense deep tissue imaging. On the other hand, because of the widely existing multidrug resistance (MDR) of tumor cells, traditional tumor chemotherapy often fails to achieve the desired effect. Herein, a new type of 808 nm excited pure red luminescence core-shell Nd3+-sensitized NaY(Mn)F4:Yb/Er@NaYbF4:Nd UCNPs (CSUCNPs) was designed and synthesized for deep tissue imaging and MDR tumor diagnosis with a minimized heating effect. In the meanwhile, d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) coating was introduced to endow CSUCNPs with capabilities of drug loading and overcoming MDR. The in vitro cytotoxicity test revealed that CSUCNPs-TPGS-doxorubicin (D-CSUCT) had excellent MDR cancer cell killing efficacy. The in vivo test showed that D-CSUCT can target the tumor site by enhanced retention effect, and the intense luminescent signals from the tumor site in the deep tissue were detected. Generally, this work shows D-CSUCT can overcome the MDR effect, diagnose the tumor, inhibit tumor growth, and induce tumor cells necrosis and apoptosis, without causing damage to major organs and other side effects. Overall, the study demonstrates the conjugation of red-emitted UCNPs with a minimized heating effect and that the anti-MDR carrier is highly promising for developing multifunctional theranostic system with effective simultaneous diagnosis and for multidrug-resistant tumor treatment.