The Interplay between Fe3O4 Superparamagnetic Nanoparticles, Sodium Butyrate, and Folic Acid for Intracellular Transport.

Maria Teresa Cambria,Luca Pulvirenti,Concetta Federico,Fulvia Sinatra,Samuele Laudani,Giusy Villaggio,Guglielmo Guido Condorelli,Salvatore Saccone

doi:10.3390/ijms21228473

Abstract

Combined treatments which use nanoparticles and drugs could be a synergistic strategy for the treatment of a variety of cancers to overcome drug resistance, low efficacy, and high-dose-induced systemic toxicity. In this study, the effects on human colon adenocarcinoma cells of surface modified Fe3O4 magnetic nanoparticles (MNPs) in combination with sodium butyrate (NaBu), added as a free formulation, were examined demonstrating that the co-delivery produced a cytotoxic effect on malignant cells. Two different MNP coatings were investigated: a simple polyethylene glycol (PEG) layer and a mixed folic acid (FA) and PEG layer. Our results demonstrated that MNPs with FA (FA-PEG@MNPs) have a better cellular uptake than the ones without FA (PEG@MNPs), probably due to the presence of folate that acts as an activator of folate receptors (FRs) expression. However, in the presence of NaBu, the difference between the two types of MNPs was reduced. These similar behaviors for both MNPs likely occurred because of the differentiation induced by butyrate that increases the uptake of ferromagnetic nanoparticles. Moreover, we observed a strong decrease of cell viability in a NaBu dose-dependent manner. Taking into account these results, the cooperation of multifunctional MNPs with NaBu, taking into consideration the particular cancer-cell properties, can be a valuable tool for future cancer treatment.

Highlights

Colorectal cancer (CRC) and liver and lung metastasis (CLM) represent the leading causes of death in CRC patients; there is no agreed-on approach to treat CLM [1]
The present paper studied the effects on the intracellular uptake and cell vitality of the combined use of magnetic nanoparticles (MNPs) modified with two different coatings, and NaBu used as a free formulation
The present paper investigated the interplay of biocompatible MNPs modified with multifunctional layers containing or not folic acid (FA) and NaBu used as a free formulation

Summary

Introduction

Colorectal cancer (CRC) and liver and lung metastasis (CLM) represent the leading causes of death in CRC patients; there is no agreed-on approach to treat CLM [1]. Butyric acid, which is the principal source of energy for normal colonocytes, can promote growth and proliferation, while in cancerous colon cells it inhibits proliferation and induces differentiation and apoptosis [24,25,26]. For this reason, butyrate can be used in cancer therapy since it has a toxic effect on cancer cells but is beneficial for non-cancerous cells. The anti-cancer effect of butyrate has been demonstrated in cancer cell cultures and animal models of cancer [24,27,28]

Methods

Results

Conclusion