Magnetic nanoparticles for theragnostics

Abstract

Engineered magnetic nanoparticles (MNPs) represent a cutting-edge tool in medicine because they can be simultaneously functionalized and guided by a magnetic field. Use of MNPs has advanced magnetic resonance imaging (MRI), guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cell tracking and bioseparation. Integrative therapeutic and diagnostic (i.e., theragnostic) applications have emerged with MNP use, such as MRI-guided cell replacement therapy or MRI-based imaging of cancer-specific gene delivery. However, mounting evidence suggests that certain properties of nanoparticles (e.g., enhanced reactive area, ability to cross cell and tissue barriers, resistance to biodegradation) amplify their cytotoxic potential relative to molecular or bulk counterparts. Oxidative stress, a 3-tier paradigm of nanotoxicity, manifests in activation of reactive oxygen species (ROS) (tier I), followed by a pro-inflammatory response (tier II) and DNA damage leading to cellular apoptosis and mutagenesis (tier III). In vivo administered MNPs are quickly challenged by macrophages of the reticuloendothelial system (RES), resulting in not only neutralization of potential MNP toxicity but also reduced circulation time necessary for MNP efficacy. We discuss the role of MNP size, composition and surface chemistry in their intracellular uptake, biodistribution, macrophage recognition and cytotoxicity, and review current studies on MNP toxicity, caveats of nanotoxicity assessments and engineering strategies to optimize MNPs for biomedical use.

Synthesis and characterization of superparamagnetic iron-oxide nanoparticles (SPIONs) and utilization of SPIONs in X-ray imaging

“…The only metal nanoparticles approved by Food and Drug Administration are iron-oxide nanoparticles (Colombo et al 2012). Among the various nanoparticles, superparamagnetic nanoparticles (SPIONs) particularly magnetite (Fe 3 O 4 ) and maghemite (c-Fe 2 O 3 ), are researched for their resourcefulness in medical applications like theranostics, hyperthermia, drug delivery, magnet influenced radionuclide therapy, contrasting agents for imaging purposes, and MRI (Schleich et al 2013;Bolden et al 2008;Kievit and Zhang 2011;Cortajarena et al 2014;Jalilian et al 2009;Talelli et al 2009: Shubayev et al 2009Lee and Hyeon 2012). SPIONs can be used for targeted drug delivery as it can be guided through external magnets as they possess superparamagnetism, and in addition, they do not show magnetic interaction once the external magnetic field is stopped (Li et al 2016;Leder et al 2015).…”

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

“…Nanotechnology is currently an extremely active research area, and new applications are continually being developed for use as diagnostic and therapeutic agents [1]. Magnetic nanoparticles (MNP) are one of the most widely used nanotechnological tools in biomedicine; their nanometric size provides special features that favor the development of new applications, and they can be manipulated under the influence of an external magnetic field.…”

“…The main cause of the toxic effects of MNP is excessive production of ROS (reactive oxygen species) [1], which can result in oxidative stress. As nanoparticle-induced oxidative stress can have several negative effects on cells, such as alteration of organelle structure, decreased cell viability, activation of various cell stress pathways, cell cycle impairment or apoptosis induction [29], we studied these processes in a variety of in vitro tests.…”

In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low‐frequency‐ultrasound‐induced blood–brain barrier opening in swine

“…The contrast agent is then measured directly, and drug delivery is determined based on its concentration on the contrast agent (12,13). The second method assesses therapeutic agent delivery to the brain more accurately, and SPIO nanoparticles have many advantages in this regard: (i) SPIO nanoparticles are biocompatible and can be degraded safely by macrophages/ microglia (14), whereas gadolinium leakage raises safety concerns related to neurotoxicity (15); (ii) SPIO nanoparticle surfaces can be modified to easily conjugate therapeutic agents (12,13); (iii) MRI techniques such as T 2 *-weighted imaging or transverse relaxation rate (R 2 ) maps can be used to quantify the iron concentration in tissues, making quantification of therapeutic agent delivery easier (12,13); (iv) SPIO nanoparticles have high spin-spin relaxivities and can generate high magnetic moments that can be actively manipulated by externally applied magnets, making them suitable for use with magnetic targeting (16,17). The above advantages makes the SPIO nanoparticles has the potential to serve a ''thernostic'' agent, which means that the diagnostic and therapeutic functions can be concurrently provided during drug-delivering process.…”