'All-in-One' Micro- and Nanoscale MOFs for Combined Chemo-Radionuclide Therapy of Breast Cancer.

Combined chemo-radionuclide therapy offers a promising strategy to improve cancer treatment by integrating various therapeutic mechanisms within a single drug delivery system (DDS). Metal-organic frameworks (MOFs), owing to their porous structure and tunable physicochemical properties, provide a unique platform for development of multifunctional DDSs. In this study, micro- and nanoscale UiO-66-NH2 MOFs (mMOFs and nMOFs) were developed as 'all-in-one' DDSs for delivery of α-emitting radionuclide radium-223 (223Ra) and chemotherapeutic drug doxorubicin (DOX). The developed MOFs exhibited an octahedral morphology with sizes of ∼0.5 to 1 μm (DOX@mMOF) and ∼200 to 300 nm (DOX@nMOF). They demonstrated a high cellular uptake with no pronounced cytotoxicity (>90% at 4 mg/mL). In vivo biodistribution studies demonstrated high tumor retention of the developed DDSs. Importantly, combined 223Ra/DOX@mMOF and 223Ra/DOX@nMOF treatment resulted in significant tumor growth inhibition (61.2-72.1%). Histological and blood biochemical analyses revealed no detectable pathological changes. Overall, the developed UiO-66-NH2-based DDSs displayed enhanced antitumor efficacy and demonstrated their potential for combined chemo-radionuclide therapy.