Hyaluronic acid functionalized citric acid dendrimer/UiO-66-COOH as a stable and biocompatible platform for daunorubicin delivery

Abstract

This work aimed to prepare a new system for daunorubicin (DNR) delivery to improve therapeutic efficiency and decrease unwanted side effects. Typically, at first, a carboxylic acid functional group containing metal-organic framework (UiO-66-COOH) was synthesized in a simple way. Then, a third generation of citric acid dendrimer (CAD G3) was grown on it (UiO-66-COOH-CAD G3). Finally, the system was functionalized with pre-modified hyaluronic acid (UiO-66-COOH-CAD-HA). SEM analysis displayed that the synthesized particles have a spherical shape with an average particle size ranging from 260 to 280 nm. An increase in hydrodynamic diameter from 223 nm for UiO-66-COOH to 481 nm for UiO-66-COOH-CAD-HA is a sign of success in the performed reactions. Also, the average pore size was calculated at about 4.04 nm. The DNR loading efficiency of UiO-66-COOH-CAD-HA was evaluated at ∼74 % (DNR@UiO-66-COOH-CAD-HA). It was observed that the drug release rate at a lower pH is more than higher pH. The maximum hemolysis of <3 % means that the UiO-66-COOH-CAD-HA is hemocompatible. The use of DNR-loaded UiO-66-COOH-CAD-HA led to cell-killing of 77.9 % for MDA-MB 231. These results specified the great potential of UiO-66-COOH-CAD-HA for tumor drug delivery, so it could be proposed as a new carrier for anticancer agents to minimize adverse effects and improve therapeutic efficacy.