Tumor-Responsive Upconversion Nanoparticles with Tunable Degradability and Ultrabright Emission for Optical Bioimaging

Rare earth (RE)-based inorganic upconversion nanoparticles (UCNPs) have huge potency for applications varying from bioimaging to theranostics of tumors. For these applications, it is of great importance that UCNPs be expelled innocuously from a living body during a rational period of time after executing their diagnostic and/or therapeutic tasks. Despite great efforts to modulate biodegradability, a reasonable biodegradation rate for currently available UCNPs in weakly alkaline physiochemical buffers has not yet been realized. Herein, to achieve a tunable biodegradation rate for UCNPs, a class of core–shell-structured nanoparticles is invented by heteroepitaxially growing a CaF2:Yb shell with varying Zr4+ doping content on a biodegradable Na3ZrF7:Yb,Er core. The CaF2:Yb,Zr shell can not only enhance the emission intensity but also ensure the overall biodegradation of the nanocrystals. The degradation rate of core–shell UCNPs can be easily modulated by changing the Zr4+ doping content in the shell, and the degradation rate is pH-responsive; thus, tumor acidity-triggered degradation can be realized. When sodium alginate (SA)-modified UCNPs are used for the bioimaging of tumors, the intracellularly degraded metal ions and the released SA molecules can self-assemble through a coordination cross-linking effect, thereby improving the tumor retention of the nanosystems. These discoveries will unequivocally promote the future clinical applications of RE-based UCNPs.