A drug delivery system based on nanocomposites constructed from metal-organic frameworks and Mn3O4 nanoparticles: Preparation and physicochemical characterization for BT-474 and MCF-7 cancer cells

Abstract

An integrated nanocomposite system comprising of manganese oxide (Mn3O4) nanoparticles, functioning as a tumor diagnostic agent, in conjunction with polyacrylic acid (PAA) and ZIF-8, as pH-sensitive drug delivery agents, and methotrexate (MTX), operating as a tumor biomarker and a therapeutic agent (dual mechanism of action), is applied for both diagnostic intentions and controlled delivery of the drug. Physicochemical characteristics of the constructed system, Mn3O4@PAA@ZIF-8/MTX, are investigated by several methods, including X-ray diffraction, Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, and electrochemical techniques. The in-vitro magnetic resonance imaging measurements was performed to show the efficiency of Mn3O4@PAA@ZIF-8 nanocomposite as a contrast agent where a relaxivity (r1) of 3.3 mM−1 s−1 is found. The loading ratio was found as 161 % which is four times larger than the value obtained for Mn3O4@PAA system in the same conditions, indicating high capability of the system for MTX delivery. The application of the nanocomposite as a dual pH-sensitive nanocarrier for MTX is studied through in-vitro drug release experiments at pHs of 5.4, 6.8 and 7.4. Interestingly, the results show that a large amount of loaded MTX drug (53 %) is released from the system during incubation and dialysis at pH 5.4, compared with that (20 % and 15 %), respectively, released at pHs 6.8 and 7.4 at the same conditions. The affinity of Mn3O4@PAA@ZIF-8/MTX nanocomposite for capturing of BT-474 and MCF-7 cancer cells was evaluated via impedance spectroscopy measurements. The results show that GC-Mn3O4@PAA@ZIF-8/MTX electrode captures the BT-474 and MCF-7 cancer cells, respectively, by factors of ∼2 and 196 compared with L929 normal cells. This affinity also shows the high selectivity of the system for MCF-7 cancer cells compared with BT-474. © 2021 Elsevier B.V.