Delivery of oxaliplatin to colorectal cancer cells by folate-targeted UiO-66-NH2

Alireza Hashemzadeh; Forouzan Amerizadeh; Fereshteh Asgharzadeh; Majid Darroudi; Amir Avan; Seyed Mahdi Hassanian; Mohammad Landarani; Majid Khazaei

doi:10.1016/j.taap.2021.115573

Delivery of oxaliplatin to colorectal cancer cells by folate-targeted UiO-66-NH₂

Toxicol Appl Pharmacol. 2021 Jul 15:423:115573. doi: 10.1016/j.taap.2021.115573. Epub 2021 May 13.

Authors

Alireza Hashemzadeh¹, Forouzan Amerizadeh², Fereshteh Asgharzadeh³, Majid Darroudi⁴, Amir Avan², Seyed Mahdi Hassanian⁵, Mohammad Landarani⁶, Majid Khazaei⁷

Affiliations

¹ Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.
² Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.
⁶ Faculty of chemistry, Shahid Beheshti University, Evin, 1983963113, Tehran, Iran.
⁷ Department of Medical Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Khazaeim@mums.ac.ir.

PMID: 33991535
DOI: 10.1016/j.taap.2021.115573

Abstract

Oxaliplatin is being used in different malignancies and several side effects are reported for patients taking Oxaliplatin, including peripheral neuropathy, nausea and vomiting, diarrhea, mouth sores, low blood counts, fatigue, loss of appetite, etc. Here we have developed a targeted anticancer drug delivery system based on folate-conjugated amine-functionalized UiO-66 for the delivery of oxaliplatin (OX). UiO-66-NH₂ (U) and UiO-66-NH₂-FA(FU) were pre-functionalized by the incorporation of folic acid (FA) into the structure via coordination of the carboxylate group of FA. The FTIR spectra of drug-loaded U and FU showed the presence of new carboxylic and aliphatic groups of OX and FA. Powder X-ray diffraction (PXRD) patterns were matched accordingly with the reference pattern and FESEM results showed semi-spherical particles (115-128 nm). The evaluated amounts of OX in U and FU were calculated 304.5 and 293 mg/g_, respectively. The initial burst release of OX was 15.7% per hour for U(OX) and 10.8% per hour for FU(OX). The final release plateau gives 62.9% and 52.3% for U(OX) and FU(OX). To evaluate the application of the prepared delivery platform, they were tested on colorectal cancer cells (CT-26) via MTT assay, cell migration assay, and spheroid model. IC₅₀ values obtained from MTT assay were 21.38, 95.50, and 18.20 μg/mL for OX, U(OX), and FU(OX), respectively. After three days of treatment, the CT26 spheroids at two doses of 500 and 50 μg/mL of U(OX) and FU(OX) showed volume reduction. Moreover, the oxidative behavior of the prepared systems within the cell was assessed by total thiol, malondialdehyde, and superoxide dismutase activity. The results showed that FU(OX) had higher efficacy in preventing the growth of CT-26 spheroid, and was more effective than oxaliplation in cell migration inhibition, and induced higher oxidative stress and apoptosis.

Keywords: Metal-organic framework; microporous nanomaterials; smart drug delivery system host-guest interactions.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / administration & dosage
Amino Acids / metabolism
Animals
Cell Line, Tumor
Colorectal Neoplasms / drug therapy
Colorectal Neoplasms / metabolism*
Drug Delivery Systems / methods*
Folic Acid / administration & dosage
Folic Acid / metabolism*
Mice
Mice, Inbred BALB C
Organometallic Compounds / administration & dosage
Organometallic Compounds / metabolism*
Oxaliplatin / administration & dosage
Oxaliplatin / metabolism*
Phthalic Acids / administration & dosage
Phthalic Acids / metabolism*

Substances

Amino Acids
Organometallic Compounds
Phthalic Acids
UiO-66
Oxaliplatin
Folic Acid