LAUSR

Abstract The development of efficient drug delivery and imaging approaches is of great importance for both diagnostic and therapeutic purposes. This is especially important for the triple-negative breast cancers for which chemotherapy is often the mainstay of treatment. Metal-organic frameworks (MOFs) have recently attracted tremendous attention as nanocarriers that can be loaded with a wide variety of therapeutic as well as bioimaging agents. Herein, the Fe3O4 core UiO-66-NH2 MOF shell nanostructures, Fe3O4@MOF, were loaded with the anticancer drug doxorubicin (DOX), and the loaded nanostructures were conjugated to highly fluorescent carbon dots (CDs) and then capped with the nucleolin-binding aptamer, AS1411. The Fe3O4@MOF-DOX-CDs-Apt nanocarriers were specifically unlocked in the presence of the nucleolin-overexpressing cancer cells, resulted in the release of the loads. The drug delivery process rendered more efficient by pH-dependent controlled release kinetics that provides an enhanced therapeutic outcome. The stimuli-responsive drug delivery system reveals a rather selective permeation of the Fe3O4@MOF-DOX-CDs-Apt nanocarriers into the triple-negative MDA-MB-231 human breast cancer cells, compared to the normal HUVEC cells. Cytotoxicity experiments revealed that the nanocarriers inhibit cell proliferation and induce selective apoptosis towards the MDA-MB-231 cancer cells (>77% at 24 ​h); whereas, less than 10% apoptosis was induced in the normal HUVEC cells. In addition, we encapsulated CDs into the nanocarriers, thereby, the nanocarriers exhibit fluorescence imaging functionality, thus can effectively contribute to monitoring biodistribution of the nanocarriers in vitro. Based on these findings, the Fe3O4@MOF-DOX-CDs-Apt nanocarriers can serve as a promising multifunctional material for cancer therapy and cellular bioimaging.