Heterodimers Made of Metal-Organic Frameworks and Upconversion Nanoparticles for Bioimaging and pH-responsive Dual-drug Delivery
Developing multifunctional nanocomposite for pH-responsive controlled dual-drug delivery is still a huge challenge. Here we report a gentle and simple method to grow metal-organic frameworks (MOFs) that can load two anticancer drugs, DOX and 5-FU (Doxorubicin and 5-Fluorouracil), on the surface of upconversion nanoparticles (UCNPs) by reactions of Schiff base and electrostatic adsorption. The resulting pH-responsive UCMOFs@D@5 nanosystems show effective dual-drug release by cleavage of chemical bond and disruption of the MOFs structure under acidic conditions. Moreover, the final nanosystems UCMOFs@D@5 show much higher cytotoxicity in comparison with UCMOFs@D and UCMOFs@5 that loaded only one kind of drug, respectively, after being incubated with human cervical cancer (HeLa) cells, indicating that the Dox and 5-FU released from final nanosystems have synergistic effects on cytotoxicity. Cellular uptake studies show UCMOFs@D@5 can be well uptaken by HeLa cells and have potential bioimaging applications for intracellular fluorescence imaging with high-contrast, and beneficial for intracellular localization of anti-cancer drug. In addition, the nanosystems can be successfully applied for T1-weighted magnetic resonance imaging. Therefore, we developed a visualized tracking agent combined with MOFs to load two anticancer drugs to form the nanosystems for diagnosis and synergistic treatment, thus achieving the bioimaging and stimulation-responsive dual-drug release.