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 (r(1)) 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 similar to 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.