Enhanced accumulation of theranostic nanoparticles in brain tumor by external magnetic field mediated in situ clustering of magnetic nanoparticles

Abstract

Magnetic iron oxide nanoparticles (MIONs) have received much attention due to their unique properties such as ferromagnetic and superparamagnetic characters. These magnetic properties enable the broad use of MIONs in biomedical applications including magnetic resonance imaging (MRI), magnetically guided delivery, and hyperthermal therapy. In particular, magnetic field guided delivery systems have shown promising potential in the development of targeted drug delivery systems for brain tumors. This system facilitates the extravasation and accumulation of MIONs within the brain tumor under external magnetic field. However, the practical use of MIONs is highly limited due to the large physical size of MIONs required for the sufficient retention and accumulation of particles in the brain tumor. This study aims to enhance the accumulation and retention of MIONs in the brain tumor by in situ formation of large clusters of MIONs. To achieve this goal, MIONs with core size of 100 nm were modified with free thiol end groups by conjugating bi-functional poly(ethylene glycol) (NHS-PEG-SH). It is expected that the prepared MIONs-PEG-SH remain stable during the systemic circulation. When the circulating MIONs-PEG-SH are exposed to the external magnetic field applied to the brain tumor, the local concentration of MIONs-PEG-SH can be increased and subsequent interactions among MIONs induce a disulfide bond formation. As a result, in situ formation of the large clusters of MIONs allows enhanced accumulation and retention of MIONs in a rat brain tumor model. Moreover, when doxorubicin is loaded onto the MIONs, the biodistribution of doxorubicin at brain tumor site is highly enhanced, suggesting their potential use in theranostic applications. (C) 2017 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.