Ultrasmall-Superbright Neodymium-Upconversion Nanoparticles via Energy Migration Manipulation and Lattice Modification: 808 nm-Activated Drug Release.

Nd3+-sensitized upconversion nanoparticles are among the most promising emerging fluorescent nanotransducers. They are activated by 808 nm irradiation, which features merits such as limited tissue overheating and deeper penetration depth, and hence are attractive for diagnostic and therapeutic applications. Recent studies indicate that ultrasmall nanoparticles (<10 nm) are potentially more suitable for clinical application due to their favorable biodistribution and safety profiles. However, upconversion nanoparticles in the sub-10 nm range suffer from poor luminescence due to their ultrasmall size and greater proportion of lattice defects. To reconcile these opposing traits, we adopt a combinatorial strategy of energy migration manipulation and crystal lattice modification, creating ultrasmall-superbright Nd3+-sensitized nanoparticles with 2 orders of magnitude enhancement in upconversion luminescence. Specifically, we configure a sandwich-type nanostructure with a Yb3+-enriched intermediate layer [Nd3+]-[Yb3+-Yb3+]-[Yb3+-Tm3+] to form a positively reinforced energy migration system, while introducing Ca2+ into the crystal lattice to reduce lattice defects. Furthermore, we apply the nanoparticles to 808 nm light-mediated drug release. The results indicate time-dependent cancer cells killing and better antitumor activities. These ultrasmall-superbright dots have unraveled more opportunities in upconversion photomedicine with the promise of potentially safer and more effective therapy.