Synthesis of multifunctional upconversion NMOFs for targeted antitumor drug delivery and imaging in triple negative breast cancer cells

Abstract

Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 lacking triple negative breast cancers (TNBC) are the leading cause of death. The successful transport of chemotherapeutics in TNBC with receptor mediated targeting and image guided treatment is a serious challenge for cancer therapy. In this work, folic acid encapsulated nanoscale metal organic framework (NMOFs) is developed on the surface of upconversion nanoparticles (UCNPs) as a targeted and pH responsive anticancer drug carrier. To construct the assembled core-shell drug delivery system (DDS), NaYF4: Yb3+, Er3+ is taken as UCNPs for its outstanding luminescence properties, then a folic acid encapsulated NMOFs based on tetravalent metal Zr (IV) is directly developed on UCNPs [labeled as UCNP@UIO-66(NH2)/FA]. Excitingly, UCNP@UIO-66(NH2)/FA are nontoxic towards TNBC cells (MDA-MB-468) and normal cell lines (NIH3T3). The anticancer drug doxorubicin (DOX) is encapsulated into UCNP@UIO-66(NH2)/FA with high drug loading efficiency (1.42g DOX per g NMOFs) and shows pH responsive drug release. The DOX loaded UCNP@UIO-66(NH2)/FA successfully enters into the MDA-MB-468 cells through a folate receptor mediated endocytosis and exhibits a higher cytotoxicity than normal cells. Flow cytometry and nuclear apoptosis studies suggest the present DDS can be potential applicable in breast cancer therapy to reduce the side effects.