PH-Responsive Charge-Conversional and Hemolytic Activities of Magnetic Nanocomposite Particles for Cell-Targeted Hyperthermia.

Md Abdur Rahman,Yoshimasa Matsumura,Shigekazu Yano,Bungo Ochiai

doi:10.1021/acsomega.7b01918

Md Abdur Rahman, Yoshimasa Matsumura + Show 2 more

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https://doi.org/10.1021/acsomega.7b01918

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Journal: ACS omega	Publication Date: Jan 25, 2018
Citations: 12	License type: cc-by

Affiliation: Yamagata University

Abstract

Magnetic nanocomposite particle (MNP)-induced hyperthermia therapy has been restricted by inefficient cellular targeting. pH-responsive charge-conversional MNPs can enhance selective cellular uptake in acidic cells like tumors by sensing extracellular acidity based on their charge alteration. We have synthesized new, pH-induced charge-conversional, superparamagnetic, and single-cored Fe3O4 nanocomposite particles coated by N-itaconylated chitosan (NICS) cross-linked with ethylene glycol diglycidyl ether (EGDE) (Fe3O4-NICS-EGDE) using a simple, one-step chemical coprecipitation–coating process. The surface of the Fe3O4-NICS-EGDE nanocomposite particles was modified with ethanolamine (EA) via aza-Michael addition to enhance their buffering capacity, aqueous stability, and pH sensitivity. The designed Fe3O4-NICS-EGDE-EA nanocomposite particles showed pH-dependent charge-conversional properties, colloidal stability, and excellent hemocompatibility in physiological media. By contrast, the charge-conversional properties enabled microwave-induced hemolysis only under weakly acidic conditions. Therefore, the composite particles are highly feasible for magnetically induced and targeted cellular thermotherapeutic applications.

Highlights

Magnetic nanocomposite particles (MNPs) have been an attractive subject in nanotechnology and biomedicine because of their unique and promising properties
N-itaconylated chitosan (NICS) was synthesized by partial modification of the amino groups of CS with itaconic anhydride (IAn) to achieve controllable aqueous solubility and desired reactivity for further modification
The resulting compound was characterized by 1H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD, Figure S1)

Summary

Introduction

Magnetic nanocomposite particles (MNPs) have been an attractive subject in nanotechnology and biomedicine because of their unique and promising properties. Iron oxide (Fe3O4 and Fe2O3) nanocomposite particles have been applied extensively in biomedical applications, such as diagnostic contrast agents for magnetic resonance imaging (MRI),[1−8] positron emission tomography,[3] single-photon emission computed tomography,[4] drug and gene delivery,[9−29] blood detoxification,[30] and magnetic hyperthermia therapy for tumors.[18,24−26,31−43] Most antitumor drugs still present many limitations, including poor solubility, short circulation kinetics, insufficient selectivity between malignant and healthy cells, and decreasing immune responses, causing adverse side effects.[11] MNPs may offer a solution by enhancing selectivity toward target cells. The produced heat is transferred very quickly to the adjacent materials, but stays locally due to the low heat-transfer capacity of physiological fluids, such as blood, lymph, and intracellular fluids, resulting in highly focused heating.[35,36] unspecific and inadequate delivery of MNPs induces severe side effects, sublethal temperature changes, resistance in malignant cells, and damage to healthy cells.[37]

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