Magnetic Targeting of Growth Factors Using Iron Oxide Nanoparticles.

Michal Marcus,Ahmad Maswadeh,Ziv Shemesh,Menachem Motiei,Amos Sharoni,Alexandra Smith,Shlomo Margel,Hadas Schori,Idan Zak,Orit Shefi

doi:10.3390/nano8090707

Michal Marcus, Ahmad Maswadeh + Show 8 more

Open Access

https://doi.org/10.3390/nano8090707

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Journal: Nanomaterials	Publication Date: Sep 10, 2018
Citations: 47	License type: CC BY 4.0

Affiliation: Bar-Ilan University, Sheba Medical Center

Abstract

Growth factors play an important role in nerve regeneration and repair. An attractive drug delivery strategy, termed “magnetic targeting”, aims to enhance therapeutic efficiency by directing magnetic drug carriers specifically to selected cell populations that are suitable for the nervous tissues. Here, we covalently conjugated nerve growth factor to iron oxide nanoparticles (NGF-MNPs) and used controlled magnetic fields to deliver the NGF–MNP complexes to target sites. In order to actuate the magnetic fields a modular magnetic device was designed and fabricated. PC12 cells that were plated homogenously in culture were differentiated selectively only in targeted sites out of the entire dish, restricted to areas above the magnetic “hot spots”. To examine the ability to guide the NGF-MNPs towards specific targets in vivo, we examined two model systems. First, we injected and directed magnetic carriers within the sciatic nerve. Second, we injected the MNPs intravenously and showed a significant accumulation of MNPs in mouse retina while using an external magnet that was placed next to one of the eyes. We propose a novel approach to deliver drugs selectively to injured sites, thus, to promote an effective repair with minimal systemic side effects, overcoming current challenges in regenerative therapeutics.

Highlights

Effective nerve regeneration and repair following injury or neurodegenerative diseases is under an extensive study
Magnetic iron oxide nanoparticles that were labelled with the fluorescent probe rhodamine were synthesized and covalently conjugated to nerve growth factor (NGF) through a spacer arm of polyethylene glycol (Figure 1a)
Fluorescence spectra of NGF-MNPs, measured by fluorimeter, reveal an excitation peak at 559 nm and an emission peak at 579 nm in water (Figure 1d). These results show that rhodamine fluorescent properties remain, and that the particle synthesis process does not interfere with the fluorophore’s spectrum

Summary

Introduction

Effective nerve regeneration and repair following injury or neurodegenerative diseases is under an extensive study. One of the main challenges is the ability to deliver these therapeutic agents selectively to the target injured sites, to enhance drug accumulation and promote an effective repair with minimal systemic side effects [9,10,11]. Magnetic fields that are applied externally can be designed to attract the magnetic complexes to specific sites. This novel delivery approach has been recently demonstrated in several settings in different fields [16,17,18,19,20,21], e.g., the delivery of chemo- and phototherapeutics to cancerous tissues [22,23], the delivery of stem cells to injured sites [24,25]

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