Superparamagnetic Nanoparticle Clusters for Cancer Theranostics Combining Magnetic Resonance Imaging and Hyperthermia Treatment

Abstract

Superparamagnetic nanoparticles (SPIONs) could enable cancer theranostics if magnetic resonance imaging (MRI) and magnetic hyperthermia treatment (MHT) were combined. However, the particle size of SPIONs is smaller than the pores of fenestrated capillaries in normal tissues because superparamagnetism is expressed only at a particle size <10 nm. Therefore, SPIONs leak from the capillaries of normal tissues, resulting in low accumulation in tumors. Furthermore, MHT studies have been conducted in an impractical way: direct injection of magnetic materials into tumor and application of hazardous alternating current (AC) magnetic fields. To accomplish effective enhancement of MRI contrast agents in tumors and inhibition of tumor growth by MHT with intravenous injection and a safe AC magnetic field, we clustered SPIONs not only to prevent their leakage from fenestrated capillaries in normal tissues, but also for increasing their relaxivity and the specific absorption rate. We modified the clusters with folic acid (FA) and polyethylene glycol (PEG) to promote their accumulation in tumors. SPION clustering and cluster modification with FA and PEG were achieved simultaneously via the thiol-ene click reaction. Twenty-four hours after intravenous injection of FA- and PEG-modified SPION nanoclusters (FA-PEG-SPION NCs), they accumulated locally in cancer (not necrotic) tissues within the tumor and enhanced the MRI contrast. Furthermore, 24 h after intravenous injection of the NCs, the mice were placed in an AC magnetic field with H = 8 kA/m and f = 230 kHz (Hf = 1.8×109 A/m∙s) for 20 min. The tumors of the mice underwent local heating by application of an AC magnetic field. The temperature of the tumor was higher than the surrounding tissues by ≈6°C at 20 min after treatment. Thirty-five days after treatment, the tumor volume of treated mice was one-tenth that of the control mice. Furthermore, the treated mice were alive after 12 weeks; control mice died up to 8 weeks after treatment.

Preparation and Evaluation of Iron Oxide Nanoparticles for Treatment of Iron Deficiency Anemia

“…Similar results were reported previously [17]. The zeta potentials of chitosan-coated iron oxide nanoparticles and folic acid-coated iron oxide nanoparticles are higher than that of uncoated iron oxide nanoparticles due to the highly positive charge of chitosan and folic acid [21]. fig.…”

Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)Responsive Coating and Their Application in Hyperthermia and Heat-Triggered Drug Delivery

“…12 Herein, we report a potentially generic and facile approach for the functionalization of strongly interacting cubic shaped IONPs (cubic-IONPs) via the grafting from approach using an LRP technique (reversible additionfragmentation chain transfer (RAFT)) polymerization. 13 Although several reports on functionalization of spherical-IONPs (mainly prepared by co-precipitation methods) via RAFT polymerization and other LRP techniques have demonstrated the feasibility to synthesize thermo-responsive shell on top of IONPs, [14][15][16][17][18][19][20] the protocols previously developed have mainly used nanoparticles showing superparamagnetic behavior at room temperature. These nanoparticles are, by their nature, non-interacting particles, as they miss any remanence magnetization at room temperature and in absence of an external magnetic 3 field.…”

Development Status in the Meadow of Nanostructure Magnetic Drug Delivery System and Its Promising Applications

“…It has been documented that an interactive therapy shows synergistic effect, additive effect or antagonistic effect and theranostics [20]. Magnetic nanoparticles coated with polyethene glycol which avoid the identification or capture by reticuloendothelial system, due to opsonin absorbance onto magnetic nanoparticles and phagocytosis carried out by macrophagic cells [21][22]. Antibody targeting of tumour-associated antigens or cell surface protein like tumor necrosis factor receptor enhances the selectivity or targeting effect in cancer tissues like renal cell carcinoma [23].…”