Fabrication of a biocompatible & biodegradable targeted theranostic nanocomposite with pH-Controlled drug release ability

Abstract

Here we report synthesis and characterization of a biocompatible and biodegradable nanocomposite based on paramagnetic Mn-ZnO NPs as a tumor diagnostic agent, coated with polyacrylic acid, decorated and loaded with folic acid and doxorubicin, Mn-ZnO@PAA/FOA(Dox)(load). The Mn-ZnO NPs were prepared under the coupled microwave-hydrothermal controlled conditions, leading to 42.00 +/- 3.00 nm paramagnetic Mn-ZnO NPs, appropriating for theranostic applications. The several surface, solution, and electrochemical techniques approved successful fabrication of the nanocomposite. The application of nanocomposite was tested for A2780 cancer cells. In effect, the in-vitro MRI measurements, the drug release experiments, and the MTT assay, were performed, respectively, to show diagnostic efficiency, applicability of the nanocarrier as a pH-sensitive for Dox delivery, and the biocompatibility and also theranostic efficiency of the targeted nanocomposite system. The quantitative results obtained through in-vitro tests showed that the system has potential application as a contrast agent in MRI with relaxivity (r(1)) of 35 mM(-1) s(-1) for Mn-ZnO NPs in the Mn concentration range of 0.06-0.52, which are significantly improved, compared with our previous works. The Dox drug was released from the system more efficient and faster at pH 5.4 than 7.4, supporting the pH sensitivity of nanocarrier. The in-vitro biocompatibility studies showed that the Mn-ZnO@PAA/FOA NPs (having no Dox) are not toxic, while the Mn-ZnO@PAA/FOA(Dox)(load) NPs inhibited proliferation of the A2780 cancer cells more effectively, compared with HFFF2 normal cells. Based on the electrochemical impedance spectroscopy results, the Mn-ZnO@PAA/FOA (Dox)load NPs capture the A2780 cells significantly larger than the HFFF2 cells.