Redox-responsive tumor targeted dual-drug loaded biocompatible metal\u2013organic frameworks nanoparticles for enhancing anticancer effects

Chang Liu,Xiaoyu Xu,Dongqing Wang,Hongbo Zhang,Jiaqi Yan,Junnian Zhou

doi:10.1186/s42833-020-00013-y

Abstract

Metal–organic frameworks (MOFs) have proven to be a promising class of drug carriers due to their high porosity, crystalline properties with defined structure information, and abundant surface chemistry for further functionalization. However, there has not been extensive research on MOF-based drug carriers with stimuli-responsive, dual-drug delivery, and tumor targeting functions. Here, we demonstrate the strategy of constructing a redox responsive and tumor-targeted MOF as dual-drug carrier by anchoring functional disulfide anhydride and folic acid molecules to the organic links of MOFs, respectively. The MOF composites show the controlled release of loaded 5-fluorouracil (5-FU) entrapped within UiO-66-NH2 nanostructures modified with dichloroacetic acid, which acts as a synergistical drug to 5-FU in cancer cells. In addition, the overexpressed GSH in cancer cells attacks the thiolate moiety and is oxidized in the process as it cleaves the disulfide bonds, thereby achieving redox stimuli-responsive drugs release in MOFs. The confocal laser scanning microscopy further proved that conjugation of folic acid to the MOF surface can significantly enhance the targeting uptake of cancer cells. This work paves the way to the construction of stimuli responsive tumor-targeted Nano MOF based drug carriers with potential for cancer therapies.

Highlights

The increasing incidence and mortality of cancer over the past few decades has challenged current drug treatments
For dichloroacetic acid (DCA)-UiO66-NH2, when the molar ratio of Z r4+, NH2-H2BDC, and DCA was 1:1:9, the particle size of the obtained product was around 50 nm, as characterized by transmission electron microscopy (TEM), which is superior to most Metal–organic frameworks (MOFs)-based targeted drug carriers reported in the literature
The Fourier-transform infrared spectroscopy (FT-IR) spectra of DCA-UiO-66-NH2 showed a new band in the carboxylic acid region but shifted compared to free DCA, which was characteristic of the carboxylic acid in DCA that connected to the Z r6 units

Summary

Introduction

The increasing incidence and mortality of cancer over the past few decades has challenged current drug treatments. For DCA-UiO66-NH2, when the molar ratio of Z r4+, NH2-H2BDC, and DCA was 1:1:9, the particle size of the obtained product was around 50 nm, as characterized by transmission electron microscopy (TEM) (see Additional file 1: Fig. S1a), which is superior to most MOF-based targeted drug carriers reported in the literature.

Results

Conclusion