Biodegradable Inorganic Upconversion Nanocrystals for In Vivo Applications

Lanthanide-doped inorganic upconversion nanocrystals (UCNCs) are promising as fluorescent diagnostic and therapeutic agents for in vivo applications ranging from biological imaging to disease theranostics. However, all currently available lanthanide-doped inorganic UCNCs are not biodegradable and thus cannot be harmlessly eliminated from the body of living organism during a reasonable period of time, making their clinical translations nearly impossible. Here, we report a class of redemitting biodegradable UCNCs based on Yb3+/Er3+-doped inorganic potassium heptafluozirconate (K3ZrF7:Yb/Er) that features a dynamically "soft" crystal lattice containing watersoluble [ZrF7](3)- cluster and a IC cation. The red-emitting K3ZrF7:Yb/Er UCNCs exhibit a pH-dependent biodegradation capability upon exposure to water both in vitro and in vivo, and the rapid biodegradation rate, monitored using the intrinsic red upconversion luminescence, can be tuned particularly in a mild acidic tumor microenvironment (pH similar to 5-6). More importantly, the final biodegradation products of K3ZrF7:Yb/Er UCNCs can be excreted from the body of mice in a short period of time with no evidence of toxicity, in stark contrast to the nondegradable beta-NaYF4:Yb/Er UCNCs that primarily accumulate in the main organs of mice. These findings described here unambiguously would benefit the future biomedical applications and clinical translations of lanthanide-doped inorganic UCNCs.