Functional Magnetic Core-Shell System-Based Iron Oxide Nanoparticle Coated with Biocompatible Copolymer for Anticancer Drug Delivery.

Thai Hoang Thi,Ki Park,Hieu Vu-Quang,Dai Nguyen,Long Bach,Diem-Huong Nguyen Tran,Duy Nguyen

doi:10.3390/pharmaceutics11030120

Abstract

Polymer coating has drawn increasing attention as a leading strategy to overcome the drawbacks of superparamagnetic iron oxide nanoparticles (SPIONs) in targeted delivery of anticancer drugs. In this study, SPIONs were modified with heparin-Poloxamer (HP) shell to form a SPION@HP core-shell system for anticancer drug delivery. The obtained formulation was characterized by techniques including transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), vibration sample magnetometer (VSM), proton nuclear magnetic resonance (1H-NMR), and powder X-ray diffraction (XRD). Results showed the successful attachment of HP shell on the surface of SPION core and the inability to cause considerable effects to the crystal structure and unique magnetic nature of SPION. The core-shell system maintains the morphological features of SPIONs and the desired size range. Notably, Doxorubicin (DOX), an anticancer drug, was effectively entrapped into the polymeric shell of SPION@HP, showing a loading efficiency of 66.9 ± 2.7% and controlled release up to 120 h without any initial burst effect. Additionally, MTT assay revealed that DOX-loaded SPION@HP exerted great anticancer effect against HeLa cells and could be safely used. These results pave the way for the application of SPION@HP as an effective targeted delivery system for cancer treatment.

Highlights

Tumor-targeted drug delivery utilizing nanocarriers has emerged as a promising approach for cancer treatment [1,2,3]
The fabrication of the superparamagnetic iron oxide nanoparticles (SPIONs)@HP core-shell system was performed by decorating HP polymeric shell onto the surface of SPION core prepared by the co-precipitation method (Figure 1)
Heparin-Poloxamer is a graft copolymer comprising of a backbone of heparin polymer to which a number of Poloxamer sequences are randomly grafted onto heparin via the coupling of carboxyl groups of heparin and amino groups of Poloxamer-NH2. 1H-NMR spectroscopy was employed to characterize the structure of the synthesized HP copolymer

Summary

Introduction

Tumor-targeted drug delivery utilizing nanocarriers has emerged as a promising approach for cancer treatment [1,2,3]. Despite the great potentials in the chemotherapy of many drug delivery systems (DDS), magnetic nanoparticle (MNP), especially SPION, is the primary choice for the delivery of anticancer drugs as they are feasible to effectively target cancer cells upon the manipulation of an external magnetic field, improving the therapeutic efficacy of the drug [4,5,6,7] Their superparamagnetic property allows for simultaneously treating and monitoring the tumor progression using hyperthermia therapy and magnetic resonance imaging (MRI) [8,9]. The system showed an average size of 110 ± 15 nm, excellent cellular uptake efficacy, and good anticancer activity [12] Both Poloxamer and heparin have potential features for surface engineering of SPIONs applied in cancer treatment. Cytotoxicity assay was performed to test the biocompatibility and anticancer activity of DOX-loaded SPION@HP

Materials

Characterizations

Drug Loading and In Vitro DOX Release Study

Cytotoxicity Study

Results and Discussion