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@UI0-66(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 (1.42 g DOX per g NMOFs) and shows pH responsive drug release. The DOX loaded UCNP@UI0-66(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. (C) 2017 Elsevier B.V. All rights reserved.