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Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.

ABSTRACT: 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 (T g) 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.

SUBMITTER: Hayashi K

PROVIDER: S-EPMC4063981 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.

Hayashi Koichiro K Nakamura Michihiro M Miki Hirokazu H Ozaki Shuji S Abe Masahiro M Matsumoto Toshio T Sakamoto Wataru W Yogo Toshinobu T Ishimura Kazunori K

Theranostics 20140607 8

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 (T g) of 44°C, which contains clustered Fe3O4 N ...[more]

PMID: 24955144

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Project description:Magnetically soft-soft MnFe2O4-Fe3O4 core-shell nanoparticles were synthesized through a seed-mediated method using the organometallic decomposition of metal acetyl acetonates. Two sets of core-shell nanoparticles (S1 and S2) of similar core sizes of 5.0 nm and different shell thicknesses (4.1 nm for S1 and 5.7 nm for S2) were obtained by changing the number of nucleating sites. Magnetic measurements were conducted on the nanoparticles at low and room temperatures to study the shell thickness and temperature dependence of the magnetic properties. Interestingly, both core-shell nanoparticles showed similar saturation magnetization, revealing the ineffective role of the shell thickness. In addition, the coercivity in both samples displayed similar temperature dependencies and magnitudes. Signatures of spin glass (SG) like behavior were observed from the field-cooled temperature-dependent magnetization measurements. It was suggested to be due to interface spin freezing. We observed a slight and non-monotonic temperature-dependent exchange bias in both samples with slightly higher values for S2. The effective magnetic anisotropy constant was calculated to be slightly larger in S2 than that in S1. The magnetothermal efficiency of the chitosan-coated nanoparticles was determined by measuring the specific absorption rate (SAR) under an alternating magnetic field (AMF) at 200-350 G field strengths and frequencies (495.25-167.30 kHz). The S2 nanoparticles displayed larger SAR values than the S1 nanoparticles at all field parameters. A maximum SAR value of 356.5 W/g was obtained for S2 at 495.25 kHz and 350 G for the 1 mg/mL nanoparticle concentration of ferrogel. We attributed this behavior to the larger interface SG regions in S2, which mediated the interaction between the core and shell and thus provided indirect exchange coupling between the core and shell phases. The SAR values of the core-shell nanoparticles roughly agreed with the predictions of the linear response theory. The concentration of the nanoparticles was found to affect heat conversion to a great extent. The in vitro treatment of the MDA-MB-231 human breast cancer cell line and HT-29 human colorectal cancer cell was conducted at selected frequencies and field strengths to evaluate the efficiency of the nanoparticles in killing cancer cells. The cellular cytotoxicity was estimated using flow cytometry and an MTT assay at 0 and 24 h after treatment with the AMF. The cells subjected to a 45 min treatment of the AMF (384.50 kHz and 350 G) showed a remarkable decrease in cell viability. The enhanced SAR values of the core-shell nanoparticles compared to the seeds with the most enhancement in S2 is an indication of the potential for tailoring nanoparticle structures and hence their magnetic properties for effective heat generation.

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Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.

Publications

Magnetically responsive smart nanoparticles for cancer treatment with a combination of magnetic hyperthermia and remote-control drug release.

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