Preparation and Characterization of Inulin Coated Gold Nanoparticles for Selective Delivery of Doxorubicin to Breast Cancer Cells

Mariano Licciardi,Cinzia Scialabba,Nicolò Mauro,Anna Li Volsi,Gaetano Giammona,Gennara Cavallaro

doi:10.1155/2016/2078315

Abstract

A novel folate-targeted gold-based nanosystem for achieving selectivity towards folate receptor (FR) positive cells is proposed, by virtue of the fact that the FR is a molecularly targeted entity overexpressed in a wide spectrum of solid tumors. A new inulin-folate derivative (INU-FA) has been synthesized to act as coating agent for 40 nm gold nanoparticles. The obtained polymer-coated gold nanoparticles (Au@INU-FA) were characterized in terms of hydrodynamic radius, shape, zeta potential, and aqueous stability and were loaded with doxorubicin (Au@INU-FA/Doxo). Its release capability was tested in different release media. The selectivity of Au@INU-FA/Doxo system towards FRs-positive cancer cells was proved by the differences in the quantitative uptake using human breast cancer MCF7 as FR-positive cells and 16HBE epithelial as noncancer cell line. Furthermore, the folate-mediated uptake mechanism was studied by FRs-blocking experiments. On the whole Au@INU-FA/Doxo was able to be preferentially internalized into MCF7 cells proving a folate-mediated endocytosis mechanism which allowed a higher and selective cytotoxic effect towards cancer cells. The cytotoxicity profile was evaluated on both cancer and noncancer cell lines, displaying that folate-mediated targeting implied advantageous therapeutic effects, such as amplified drug uptake and increased anticancer activity towards MCF7 cancer cells.

Highlights

Cancer is one of the most important human diseases, being the leading cause of mortality in the modern world, and has received significant attention focused on finding new therapeutics [1]
The selectivity of Au@inulin-folate derivative (INU-folic acid (FA))/Doxo system towards folate receptor (FR)-positive cancer cells was proved by the differences in the quantitative uptake using human breast cancer MCF7 as FR-positive cells and 16HBE epithelial as noncancer cell line
FRs are present in low or nondetectable quantities. These features have encouraged the synthesis of the new folate conjugate of inulin, INU-FA, here proposed as a coating agent for 40 nm gold nanospheres, in order to confer FR-mediated endocytosis properties to the nanosystem and to allow a higher and selective cytotoxic effect towards cancer cells

Summary

Introduction

Cancer is one of the most important human diseases, being the leading cause of mortality in the modern world, and has received significant attention focused on finding new therapeutics [1]. Conventional therapy methods in cancer, such as chemotherapy, radiation, and surgery, involve the employment of agents that do not greatly differentiate between cancerous and normal cells, leading to systemic toxicity and severe side effects. In contrast to conventional approaches, nanotechnologies may offer a less-invasive alternative, based on the development of nanoscale tumor-targeted delivery systems that allow tumorselective drug delivery by both passive and active targeting [3], reducing nonspecific cytotoxicity and enhancing the life expectancy and quality of life of the patient [4]. Targeted therapy emerged as an effective approach to overcome the lack of specificity of conventional chemotherapeutic agents [5]. Gold nanoparticles (GNPs) have emerged as promising carriers for drug delivery applications.

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