A multifunctional aminated UiO-67 metal-organic framework for enhancing antitumor cytotoxicity through bimodal drug delivery

摘要

Metal-organic frameworks (MOFs) are regarded as promising drug delivery systems (DDSs) for cancer treatment because of their unique porous structures and controlled drug release properties. Herein, we designed and constructed a new multifunctional drug carrier 5-FU/UiO-67-(NH)2-FAM/PMT (FUFP) with 5-FU/UiO-67-(NH)2 as the nanocarriers, FAM as a fluorescence imaging agent and PMT as both FA target and anti-tumor drug (5FAM = 5-carboxyfluorescein, 5-FU = 5-fluorouracil and PMT = pemetrexed). The drug carrier exhibited several functions, including co-loading drugs, targeted delivery and fluorescence imaging to enhance antitumor cytotoxicity for cancer therapy. Through fluorescence imaging and flow cytometry experiments, FUFP presented excellent fluorescence imaging and folate targeted properties to the high expression of folate receptor KB cell compared with low expression A549 cell and moderate expression HeLa cell. Meanwhile, FUFP exhibited superior anti-tumor activity compared single 5-FU and PMT group by the in vitro and vivo experiments. The biocompatibility test of FUFP indicated reasonable biosafety as no evidence of persistent toxicity in vivo was observed. FUFP has unique biological abilities in terms of pH-responsiveness, antitumor efficacy, biocompatibility, and simultaneously release hydrophobic and hydrophilic drug at the tumor site, indicating that this composite is a potential and promising carrier, in which provides a new strategy to co-deliver drugs for MOFs.

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