Modulating the Delivery of 5-Fluorouracil to Human Colon Cancer Cells Using Multifunctional Arginine-Coated Manganese Oxide Nanocuboids with MRI Properties

Abstract

5-Fluorouracil (5-FU) is one of the most prescribed drugs and the major component of chemotherapy for the treatment of colorectal cancer. In this study, we have designed arginine-functionalized manganese oxide nanocuboids (Arg@MNCs) for the effective delivery of 5-FU to colon cancer cells. Arginine was used as multifunctional agent to provide stability to MNCs, achieve high drug loading, control the release of loaded drug, and improve delivery to cancer cells. The synthesized Arg@MNCs were characterized by DLS, TEM, XRD, FTIR, XPS, TGA, and VSM analysis. The structural and morphological analysis by TEM showed cuboid-shaped MNCs with average particle size ∼15 nm. Biodegradation studies indicated that the Arg@MNCs were degraded at endolyosomal pH in 24 h while remaining stable at physiological pH. Hemolytic toxicity studies revealed the safety and nontoxic nature of the prepared MNCs. 5-FU-loaded Arg@MNCs showed significant control over the release of 5-FU, decrease in the hemolytic toxicity of loaded 5-FU but higher in vitro anticancer activity against HCT 116 and SW480 human colon cancer cells. Importantly, both the bare MNCs and Arg@MNCs showed excellent T1 and T2MR relaxivity under 3.0 T MRI scanner. Thus, the nanostructures developed in this study, i.e., 5-FU-Arg@MNCs could overcome the issues of both MNCs (stability) and 5-FU (low drug loading and nonspecificity) and may be used as a multifunctional theranostic nanocarrier for colon cancer treatment.