Folate-graphene chelate manganese nanoparticles as a theranostic system for colon cancer MR imaging and drug delivery: In-vivo examinations

Abstract

Targeted drug delivery can improve the efficiency of therapeutic and diagnostic agents and reduce their toxicity in cancer treatments. Herein, a theranostic system based on graphene oxide (GO) integrated with polydopamine (PDA), bovine serum albumin (BSA), DTPA-Mn(II) contrast agent, folic acid (FOA) targeting agent, and 5-fluorouracil (5Fu) anticancer drug is constructed to target CT-26 colon cancer cells via folate receptors (FRs) overexpressed on cancer cells. Physicochemical characteristics of the RGO-PDA-BSA/FOA-DTPA-Mn(II)/5Fu system are studied by electrochemical and UV–Vis methods. The system was studied based on (i) in-vitro and in-vivo MRI measurements to verify its efficiency as a diagnostic agent, (ii) histopathological experiments to evaluate biocompatibility of the system, (iii) ICP-OES analysis in conjunction with histopathological tests to find its biodistribution, and (iv) in-vivo experiments using CT-26 colon cells (tumoral animals) to show its ability for cancer therapy. The results show that the RGO-PDA-BSA/FOA-DTPA-Mn(II) is (i) highly promising as a contrast agent for MRI measurements (r1 ≅ 14.7 mM−1 s−1), (ii) biocompatible, (iii) selectively distributed into the CT-26 tumors compared with liver and spleen, and (iv) very effective for therapy of the colon tumors. © 2019 Elsevier B.V.