Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal-Organic Framework

Muhammad Usman Akbar; Muhammad Badar; Muhammad Zaheer

doi:10.1021/acsomega.2c04144

Programmable Drug Release from a Dual-Stimuli Responsive Magnetic Metal-Organic Framework

ACS Omega. 2022 Aug 30;7(36):32588-32598. doi: 10.1021/acsomega.2c04144. eCollection 2022 Sep 13.

Authors

Muhammad Usman Akbar^{1

2}, Muhammad Badar¹, Muhammad Zaheer²

Affiliations

¹ Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, KPK 29050, Pakistan.
² Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences (LUMS), Lahore 54792, Pakistan.

Abstract

Along with the increasing incidence of cancer and drawbacks of traditional drug delivery systems (DDSs), developing novel nanocarriers for sustained targeted-drug release has become urgent. In this regard, metal-organic frameworks (MOFs) have emerged as potential candidates due to their structural flexibility, defined porosity, lower toxicity, and biodegradability. Herein, a FeMn-based ferromagnetic MOF was synthesized from a preassembled Fe₂Mn(μ₃-O) cluster. The introduction of the Mn provided the ferromagnetic character to FeMn-MIL-88B. 5-Fluoruracil (5-FU) was encapsulated as a model drug in the MOFs, and its pH and H₂S dual-stimuli responsive controlled release was realized. FeMn-MIL-88B presented a higher 5-FU loading capacity of 43.8 wt % and rapid drug release behavior in a tumor microenvironment (TME) simulated medium. The carriers can rapidly release loaded drug of 70% and 26% in PBS solution (pH = 5.4) and NaHS solution (500 μM) within 24 h. The application of mathematical release models indicated 5-FU release from carriers can be precisely fitted to the first-order, second-order, and Higuchi models of release. Moreover, the cytotoxicity profile of the carrier against human embryonic kidney cells (HEK293T) suggests no adverse effects up to 100 μg/mL. The lesser toxic effect on cell viability can be attributed to the low toxicity values [LD₅₀ (Fe) = 30 g·kg^-1, (Mn) = 1.5 g·kg^-1, and (terephthalic acid) = 5 g·kg^-1] of the MOFs structural components. Together with dual-stimuli responsiveness, ferromagnetic nature, and low toxicity, FeMn-MIL-88B MOFs can emerge as promising carriers for drug delivery applications.