Surface modification of cobalt oxide nanoparticles using phosphonomethyl iminodiacetic acid followed by folic acid: a biocompatible vehicle for targeted anticancer drug delivery.

Sourav Chattopadhyay,Somenath Roy,Totan Ghosh,Debasis Das,Panchanan Pramanik,Sandeep Kumar Dash

doi:10.1007/s12645-013-0042-7

Abstract

The aim of our study was to prepare multifunctional, biocompatible nanoparticles for site-specific drug delivery. Hydrophilic nanoparticles with surface-adorned amine, carboxyl, or aldehyde groups, to be later used for bio-conjugation, were designed using phosphonomethyl iminodiacetic acid (PMIDA) as the coupling agent. These PMIDA-coated cobalt oxide nanoparticles (PMIDA-CoO) were further functionalized with folic acid (FA), using simple technique. The particles show excellent aqueous dispersion stability in physiological pH without any deterioration in hydrodynamic size. The cytotoxicity and internalization efficiency of these nanocarriers have been evaluated on folate receptor over expressed KB and folate receptor lower expressed KG1a cells. Anticancer drugs such as doxorubicin and methotrexate were successfully attached to the folic acid-decoded PMIDA-CoO nanoparticles by simple reactions. Anticancer drug-loaded nanoparticles (FA-PMIDA-CoO) exhibit elevated cytotoxicity and induce apoptosis in cancer cells, which were confirmed by flow cytometry. Fluorescence microscopy study shows the higher amount of internalization of the noncomplex by KB cells, which clearly demonstrated that cells overexpressing the human folate receptor internalized a higher level of these nanoparticles–folate conjugates than folate receptor-negative control cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s12645-013-0042-7) contains supplementary material, which is available to authorized users.

Highlights

The uses of nanoparticles (NPs) with functional properties have been widely used in a broad range of bio-applications, like drug and gene delivery, cell and tissue engineering, diagnostic and therapeutic purposes, etc. (Panyam and Labhasetwar 2003; Marin et al 2005)
This essential vitamin is a high-affinity ligand that enhances the differential specificity of conjugated anticancer drugs by targeting folate receptor (FR)-positive cancer cells (Leamon and Reddy 2004)
FA-phosphonomethyl iminodiacetic acid (PMIDA)-cobalt oxide (CoO) NPs were synthesized according to the method outlined in Scheme 1. –NH2 group of folic acid and carboxylic group (−COOH) of PMIDA-CoO NPs were connected through the end-amino groups

Summary

Introduction

The uses of nanoparticles (NPs) with functional properties have been widely used in a broad range of bio-applications, like drug and gene delivery, cell and tissue engineering, diagnostic and therapeutic purposes, etc. (Panyam and Labhasetwar 2003; Marin et al 2005). (Panyam and Labhasetwar 2003; Marin et al 2005) Among these applications, the field of drug delivery by NPs with specific and rapid internalization into a target cell has immense promise (Maeda et al 2009; Faraji and Wipf 2009). Folic acid is a member of vitamin B family and plays an essential role in cell survival by participating in the biosynthesis of nucleic acids (Antony 1996). This essential vitamin is a high-affinity ligand that enhances the differential specificity of conjugated anticancer drugs by targeting folate receptor (FR)-positive cancer cells (Leamon and Reddy 2004). Various types of anticancer drugs were conjugated and evaluated for their biological activity (Low and Antony 2004)

Objectives

Methods

Findings

Conclusion