Harnessing nanotechnology for breast cancer management: UiO-66 (NH2) metal-organic frameworks functionalized with chitosan and folic acid for the efficient delivery of doxorubicin

Abstract

Cancer is a leading cause of morbidity globally, which could be due to a lack of effective treatments. The inherent inadequacies of traditional medicines in terms of tumour selectivity and undesired toxicity urge us to seek alternative therapies to address these drawbacks. Metalorganic frameworks (MOFs) have been synthesized for use in drug delivery systems (DDS) because of their improved porosity and larger specific surface area. In this research, UiO-66-NH2 MOFs were synthesized via a solvothermal technique and functionalized with chitosan-folic acid (CS-FA) as a DDS for targeted doxorubicin (DOX) delivery. The MOF nanoplatforms were characterized via different techniques, including FTIR, PXRD, BET, TEM, DLS, TGA, SEM, and TGA. Remarkably, compared with the unmodified MOF, UiO-DOX@CS-FA delayed DOX release due to a gated effect induced by the CS-FA surface coating. pH-sensitive DOX release was observed, where 39.76 % of the drug was released in the tumour-mimicking pH of 5.2, whereas 5.84 % of the drug was released at physiological pH (7.4). In vitro cellular toxicity and uptake investigations demonstrated that UiO-DOX@CS-FA is a highly effective targeted DDS against MCF-7 breast cancer cells. Furthermore, in vivo toxicity studies in Wistar rats revealed no evidence of serious adverse effects. The variety of pharmacokinetic characteristics tested indicated that the bioavailability and release kinetics of DOX improved. Our findings lay the groundwork for the development and production of novel polymer conjugate-based nanoparticles with increased tumour-targeting efficacy.