Luminescent nanotherapeutics system for Real-Time imaging and Membrane-Mitochondria stepwise targeted drug delivery in ovarian cancer

Considerable attention has been devoted to developing anti-cancer treatments targeted mitochondria. However, there is a dearth of literature on using luminescent metal–organic frameworks for the transportation of anti-cancer drugs to organelles. A luminescent nanotherapeutic platform known as UiO-DOX@FA/TPP has been engineered with a membrane-mitochondrial stepwise targeting strategy for the delivery of doxorubicin (DOX). DOX administration caused mitochondrial dysfunction, increased Caspase-3 activity, and cell apoptosis. The UiO-DOX@FA/TPP system improved drug sensitivity, requiring only 10.8 % of the free DOX dose. It showed strong anti-tumor effects in vivo, with over 98 % tumor growth inhibition and commendable biocompatibility. The system also enabled in vivo imaging by emitting fluorescence at around 500 nm, highlighting its transport and targeted distribution to tumor sites. Furthermore, treating cells with UiO-DOX@FA/TPP nanosystem led to extensive gene expression changes, primarily enriched in Ca2+ signaling and autophagy regulation. The stepwise targeted luminescent UiO-DOX@FA/TPP nanosystem allow for the precise identification and delineation of ovarian cancer boundaries, monitoring of drug transport in real-time, and targeted delivery to mitochondria for inducing apoptosis. This innovative approach provides a theoretical and methodological basis for integrating ovarian cancer diagnosis and treatment.