Hyaluronic acid targeted metal organic framework based on iron (III) for delivery of platinum curcumin cytotoxic agent to triple negative breast cancer cell line

Abstract

Platinum-based drugs are an essential class of chemotherapy drugs in breast cancer. However, suffer from side effects and drug resistance; structural changes and applying drug carriers can lead to new drug candidates in this class. The metal-organic frameworks (MOFs) as porous carriers have recently attracted much attention in drug delivery. In this study, for the first time, hyaluronic acid (HA)-targeted MOF (NH2-MIL-101 (Fe)) nanoparticles (Pt-CUR@MIL@HA NPs) were evaluated in delivery of platinum-curcumin (Pt-CUR) prodrug to the MDA-MB-231 triple-negative breast cancer cell line; in this regard, the cytotoxicity, ROS production, and cellular uptake of designed NPs have been studied. Different analysis methods confirmed chemical structures, the prepared NPs had a uniform morphology, and the hydrodynamic size of the optimized non-targeted loaded particles increased to about 252 nm with a zeta potential of +26.9 mV, after targeting with HA, the size increased to 310 nm, and the zeta potential changed to −28 mV. Based on TGA and atomic absorption (ICP-MS) results, the drug loading percent was determined to be about 30%–35%. Drug release from the HA targeted Pt-CUR@MIL@HA system in the neutral condition was slow and sustained, and after 36 h, a maximum of 60% of the drug was released, but in acidic conditions, the release was increased, and by 18 h, the release was about 80%. The cytotoxicity of MOF NPs containing Pt-CUR was more significant than that of the free drug, and HA targeted has resulted in more cellular uptake than the non-targeted NPs. In conclusion, these new MOF- based HA-coated NPs of PT-CUR can be introduced to pre-clinical researches after completing in vitro and in vivo studies. © 2022 John Wiley & Sons Ltd.