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.

Magnetic nanoparticles (MNPs) generate heat when a high-frequency magnetic field (HFMF) is applied to them. Induction heat is useful not only for hyperthermia treatment but also as a driving force for drug-release. beta-Cyclodextrin (CD) can act as drug container because of its inclusion properties. Drugs incorporated in the CD can thus be released through the use of induction heating, or hyperthermic effects, by applying a HFMF. In this study, we have synthesized folic acid (FA) and CD-functionalized superparamagnetic iron oxide nanoparticles, FA-CD-SPIONs, by chemically modifying SPIONs derived from iron(III) allylacetylacetonate. FA is well-known as a targeting ligand for breast cancer tumor and endows the SPIONs with cancer-targeting capability. Immobilization of FA and CD on spinel iron oxide nanoparticles was confirmed by Fourier transform IR (FTIR) and X-ray photoelectron spectroscopy (XPS). The FA-CD-SPIONs have a hydrodynamic diameter of 12.4 nm and prolonged stability in water. They are superparamagnetic with a magnetization of 51 emu g(-1) at 16 kOe. They generate heat when an alternating current (AC) magnetic field is applied to them and have a specific absorption rate (SAR) of 132 W g(-1) at 230 kHz and 100 Oe. Induction heating triggers drug release from the CD cavity on the particle - a behavior that is controlled by switching the HFMF on and off. The FA-CD-SPIONs are noncytotoxic for cells. Thus, FA-CD-SPIONs can serve as a novel device for performing drug delivery and hyperthermia simultaneously.

We report the synthesis of smart nanoparticles (NPs) that generate heat in response to an alternating current magnetic field (ACMF) and that sequentially release an anticancer drug (doxorubicin, DOX). We further study the in vivo therapeutic efficacy of the combination of magnetic hyperthermia (MHT) and chemotherapy using the smart NPs for the treatment of multiple myeloma. The smart NPs are composed of a polymer with a glass-transition temperature (Tg) of 44°C, which contains clustered Fe3O4 NPs and DOX. The clustered Fe3O4 NPs produce heat when the ACMF is applied and rise above 44°C, which softens the polymer phase and leads to the release of DOX. The combination of MHT and chemotherapy using the smart NPs destroys cancer cells in the entire tumor and achieves a complete cure in one treatment without the recurrence of malignancy. Furthermore, the smart NPs have no significant toxicity.

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Polyamides having a photoisomerizable unsaturated linkage in the backbone of the polymer chain were synthesized in an attempt to construct photoresponsive polymer systems. Solution viscosity of polyamides composed of azobenzene and phenylenediamide residues under ultraviolet irradiation (410 > X > 350 nm) was 60% lower than the viscosity in the dark in N,iV-dimethylacetamide. The viscosity that was reduced by the irradiation returned to the initial value in 30 h at 20 °C after removing the light. The slow recovery of the viscosity in the dark was accelerated by visible light irradiation (X > 470 nm). On alternate irradiation with ultraviolet and visible light, the solution viscosity was reversibly controlled by as much as 60%. Spectroscopic study and the effect of rigidity of chain segment on the photoviscosity behavior indicate that the photodecrease arises from the trans-cis photoisomerization of the azobenzene residues in the backbone of the semiflexible chain. Photocontrols of conductivity and pH value were also achieved by using photoresponsive polyamides having terephthalic acid groups.