High‐nuclearity Luminescent Lanthanide Nanocages for Tumor Drug Delivery

Abstract There is an unmet need for easy‐to‐visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine‐based lanthanide nanocages, Eu 60 and Tb 60 (collectively Ln 60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as‐prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln 60 nanocages with diameters around 5 nm. DOX@Ln 60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln 60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln 60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln 60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.