Magnetic nanoparticle-based drug delivery for cancer therapy

Highlights

• Presentation of various magnetic drug delivery systems.

• Magnetic nano drug carriers: particles, gels, bubbles, capsules, spheres and tubes.

• The tumor specific attributes induce various tumor targeting strategies.

• Drug release is triggered by pH, temperature, redox or electrical properties.

• Clinical translation is the current need for nano drug delivery developments.

Abstract

Nanoparticles have belonged to various fields of biomedical research for quite some time. A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles which are directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so-called “magnetic drug targeting”, MDT), has additionally emerged as a promising strategy of drug delivery. Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism–exploiting, tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. As it is nearly impossible to record every magnetic nanoparticle system developed so far, this review summarizes interesting approaches which have recently emerged in the field of targeted drug delivery for cancer therapy based on magnetic nanoparticles.

Introduction

Nanotechnology has already revolutionized the energy and electronics sector, and has been deployed successfully on a commercial scale. Nanoparticles form the basis for a huge variety of pharmaceutical and medical applications, including diagnostics and drug delivery, and have special potential in cancer therapy. In 2010, the annual number of cancer incidences in the European Union reached 2.6 million, and about 1.3 million deaths from cancer were recorded [2]. The rising tendency is continuing despite all the preventive measures and therapeutic efforts of recent decades, as more and more of the European population are fortunately now surviving into old age. Conventional chemotherapy, applied systemically, lacks sufficient enrichment of the therapeutic agents in the tumor area and negatively affects the whole organism. One of the future therapeutic challenges is thus the development of directed therapy approaches which address the tumor more specifically, while sparing the remaining tissues and increasing the efficiency of the employed agents. Nanoparticles represent a promising platform for the targeted delivery of anticancer drugs. Biomimetic features, as well as an extraordinary surface-to-volume ratio make them promising tools in the therapy of human diseases [3], [4]. They display unique physical and chemical properties due to their size, which is in the same range as antibodies, receptors, nucleic acids, proteins and other biological macromolecules. Regarding therapeutic applications, drug transportation in a nanoparticle-bound form enables even less soluble or instable agents to reach tumor cells [5], [6], [7]. A multitude of different antitumor drugs can be made available via nanoparticle delivery platforms for improved localized enrichment [8]. Thus, drugs with highly effective cytotoxic potential that have not yet been applicable due to their high systemic toxicity or because of metabolic barriers can now be transported by nanoparticles and applied in vivo. For oncology purposes, this means a maximized level of antineoplastic agents in the tumor area and a minimized level in the remaining parts of the body.

A promising site-directed application in the field of nanomedicine is drug targeting using magnetic nanoparticles directed at the target tissue by means of an external magnetic field. Materials most commonly used for magnetic drug delivery contain metal or metal oxide nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs). SPIONs consist of an iron oxide core, often coated with organic materials such as fatty acids, polysaccharides or polymers to improve colloidal stability and to prevent separation into particles and carrier medium [1]. Colloidal magnetic iron oxide nanoparticles have also been implemented as contrast agents for MRI [9], [10]. Currently, the marketing and clinical application of the iron oxide-containing contrast agents are at a standstill due to economic considerations of the pharmaceutical companies. Commercially available contrast media such as Resovist^®, Endorem^®, Sinerem^® and Combidex^® have been withdrawn from the market, with the exception of the oral iron oxide contrast medium Ferumoxsil (Lumirem/Gastromark), and ferumoxytol (Rienso/Feraheme), a new IV agent approved for iron replacement therapy in chronic renal failure patients with iron-deficiency anemia. Interestingly, ferumoxytol has recently been investigated as an MR imaging agent for pancreatic inflammation due to the enhanced nanoparticle uptake by macrophages in the inflamed pancreatic lesion [11]. In general, magnetite and maghemite particles are those most commonly used in medicine and are, as a rule, well-tolerated [12], [13]. The magnetic properties of SPIONs allow the remote control of their accumulation by means of an external magnetic field, as well as their application for hyperthermia therapy. Conjugation of SPIONs with drugs, in combination with an external magnetic field to target the nanoparticles (so called “magnetic drug targeting”, MDT), has additionally emerged as a promising strategy of drug delivery [14], [15], [16]. Besides the particle size, the charge and chemical features are relevant for in vivo toxicity and must be taken into consideration prior to their application in patients.

Magnetic nanoparticle-based drug delivery is a sophisticated overall concept and a multitude of magnetic delivery vehicles have been developed. Targeting mechanism-exploiting tumor-specific attributes are becoming more and more sophisticated. The same is true for controlled-release strategies for the diseased site. Both leverage the concept of targeted treatment up to a highly selective cure utilizing multifunctional particles. It seems virtually impossible to describe every magnetic nanoparticle system developed so far. Therefore, in this review we have attempted to describe the currently most fascinating approaches in targeted drug delivery for cancer therapy based on magnetic nanoparticles since 2012.