TY - JOUR
T1 - Modulating the Delivery of 5-Fluorouracil to Human Colon Cancer Cells Using Multifunctional Arginine-Coated Manganese Oxide Nanocuboids with MRI Properties
AU - Jain, Poonam
AU - Patel, Krunal
AU - Jangid, Ashok Kumar
AU - Guleria, Anupam
AU - Patel, Sunita
AU - Pooja, Deep
AU - Kulhari, Hitesh
N1 - Publisher Copyright:
© 2020 American Chemical Society.
PY - 2020/10/19
Y1 - 2020/10/19
N2 - 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.
AB - 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.
KW - 5-fluorouracil
KW - colon cancer
KW - l -arginine
KW - magnetic resonance imaging
KW - manganese oxide
UR - http://www.scopus.com/inward/record.url?scp=85096463000&partnerID=8YFLogxK
U2 - 10.1021/acsabm.0c00780
DO - 10.1021/acsabm.0c00780
M3 - Article
AN - SCOPUS:85096463000
SN - 2576-6422
VL - 3
SP - 6852
EP - 6864
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 10
ER -