[Show abstract][Hide abstract] ABSTRACT: The abscopal effect has previously been described in various tumors and is associated with radiation therapy and hyperthermia, with possible underlying mechanisms explaining each observed case. In the present study, we aimed to investigate the antitumor effects of magnet-mediated hyperthermia on Walker-256 carcinosarcomas in rats at two different temperature ranges (42-46°C and 50-55°C). We also aimed to identify whether a higher therapeutic temperature of magnetic-mediated hyperthermia improves the abscopal antitumor effects, where localised irradiation of the tumor causes not only the irradiated tumor to shrink, but also tumors located far from the area of irradiation. Following induction of carcinosarcoma in both sides of the body, magnet-mediated hyperthermia was applied to one side only, leaving the other side as a control. The changes in tumor growth were observed. Our results demonstrated that magnet-mediated hyperthermia at a higher temperature inhibited the growth of carcinosarcoma at the site of treatment. Furthermore, the growth of the carcinosarcoma on the untreated side was also inhibited. The expression levels of proliferating cell nuclear antigen were decreased in the hyperthermia group, which was more significant in the higher temperature test group. Flow cytometric analysis showed an increased number of CD4- and CD8-positive T cells, and enzyme-linked immunosorbent assay showed increased levels of interferon-γ and interleukin-2 in the higher temperature group. These results suggested that magnet-mediated hyperthermia at a higher temperature (50-55°C) can improve the abscopal antitumor effects and stimulate a greater endogenous immune response in carcinosarcoma-bearing rats.
[Show abstract][Hide abstract] ABSTRACT: Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) can play crucial roles for medical applications such as cancer magnetic induction hyperthermia, magnetic resonance imaging, and magnetofection. Gene therapy is an emerging area of biomedicine and has the potential to revolutionize the treatment of human disease. Herein we report the results of modified magnetic nanoparticles coated with protamine containing nuclear localization signal sequences. Thermogravimetric analysis, X-ray powder diffraction, cellular uptake, and gene magnetofection efficiency of protamine modified SPIONs were evaluated. SPIONs modified with protamine resulted in more cellular uptake and higher-efficient gene transfection in HepG2 cells. The work demonstrates that protamine modified SPIONs can be used as a novel kind of highly efficient magnetic mediator for magnetic induction hyperthermia combined with gene therapy.
Journal of Nanoscience and Nanotechnology 02/2013; 13(2):746-50. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The degradation of basement membranes by tumor cells involves secretion and activation of proteinases, such as the matrix metalloproteinases (MMPs), and results from an imbalance between their inhibitors and activators that are controlled by various growth factors or cytokines, among which TGF-β1 may be the most intriguing. In order to study the therapeutic effect and molecular mechanism of hyperthermia on aggressive malignant melanoma, the expression levels of TGF-β1 and Smad4 in B16F10 cells were dynamically analyzed by RT-PCR and western blotting for 24 h after heat treatment, from which time-dependent changes were determined. As expected, the proliferation and invasive ability of B16F10 cells were suppressed strongly by heat treatment. Furthermore, we compared the expression of TGF-β1 in melanoma mouse models before and after magnetic fluid hyperthermia (MFH) in vivo. After hyperthermia, the tumor growth rate was reduced with a decline in TGF-β1 protein expression. We conclude that changes in the TGF-β1 pathway induced by hyperthermia may be an important part of the molecular mechanism involved.
[Show abstract][Hide abstract] ABSTRACT: Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. This work evaluates the effects of a kind of novel solar-planet structured magnetic nanocomposites (MNCs) for magnetic thermochemotherapy. Amino silane coated magnetic nanoparticles (MNPs) as agent of magnetic mediated hyperthermia (MMH) for cancer treatment were prepared by the chemical precipitation method. Docetaxel (an anticancer drug) loaded polymeric nanoparticles (DNPs) composed of carboxylic-terminated poly (D,L-lactic-co-glycolic acid) (PLGA) with Vitamin E TPGS as emulsifier for sustained drug release were prepared by a modified solvent extraction/evaporation technique. Furthermore, the MNPs modified with amino groups could be covalently attached to the surface of carboxylic terminated DNPs to form the so-called solar-planet structured MNCs by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking. The prepared solar-planet structure has been confirmed by fluorescent observation. Inductive heating property of the nanocomposite was evaluation by monitoring the temperature increase of the MNCs suspension under alternative magnetic field (AMF). Drug encapsulation efficacy and drug release of the magnetic nanocomposite were conducted by high performance liquid chromatography (HPLC). In vitro evaluation of the novel nanocomposite as mediator for thermochemotherapy was conducted on the U251 human glioma cells and the synergistic effect between MMH and docetaxel chemotherapy was confirmed. All the observation supports that solar-planet structured MNC is a novel and effective mediator for magnetic thermochemotherapy. The MNCs can realize cancer comprehensive treatment thus has great potential in clinical application.
Journal of Nanoscience and Nanotechnology 02/2012; 12(2):1024-31. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the effect and feasibility of hyperthermia treatment on subcutaneous pancreatic cancer in female Kunming mice, using a murine pancreatic cancer cell line (MPC-83) established by us and found in this study to originate from epithelial pancreatic acinus. Magnetic fluid (MF) with ferromagnetic particles of about 20 nm in size was used as a heating mediator. MF was injected into the subcutaneous nodules with subaxillary regions of mice 10 days after tumor transplantation; homogeneous distribution of magnetic nanoparticles in nodules was easily detected by X-ray 24 h later. Mice were allocated to four groups as follows: no treatment (control); MF injection alone; alternating magnetic field (AMF) irradiation alone; and MF injection and hyperthermia generated by applying AMF (300 kHz, 110 Gs). The two hyperthermia-treated subgroup tumors reached central temperatures of 47 and 51˚C, respectively, for 30 min; while rectal temperature in both subgroups remained below 36˚C. Tumor growth was inhibited and survival significantly prolonged in the hyperthermia group compared with other groups (P<0.05). Tumor cells near the MF in the hyperthermia group apoptosed or necrosed immediately after hyperthermia. By day 14, there were no subcutaneous nodules; and residual magnetic nanoparticles were ingested by phagocytes. Nuclear proliferating cell nuclear antigen (PCNA) decreased in hyperthermia group tumor cells compared to the other groups; cytoplasmic heat shock protein 70 (HSP 70) was conspicuously higher immediately after hyperthermia (P<0.05). This technique had therapeutic potential and provided a new idea in the treatment of pancreatic cancer.
[Show abstract][Hide abstract] ABSTRACT: The present study aimed to investigate heating-induced alterations of breast cancer cell invasion abilities and the potential mechanisms associated with TGF-β1 expression. MCF-7 cells were heated at 43, 45, 47 and 37 °C for 30 min. In vitro cell invasion ability was evaluated by matrigel invasion assay. The activity of matrix metalloproteinase (MMP)-2/9 was investigated by gelatin zymographic assays. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) was investigated by immunocytochemistry and RT-PCR. Apoptosis was analysed by flow-cytometry. The invasive potential of MCF-7 cells was reduced by heating, and MMP-2/9 secretion and enzymatic activity were suppressed. Furthermore, VEGF and TGF-β1 mRNA and proteins were suppressed by hyperthermia. These results suggest that down-regulation of the expression of TGF-β1, EGF and MMPs by hyperthermia probably accounts for the inhibition of the invasive abilities of MCF-7 cells.
[Show abstract][Hide abstract] ABSTRACT: Hyperthermia is a promising treatment for human cervical cancer. However, little is known about whether and under what conditions heat treatment exerts tumor inhibition effects on cervical cancer, and the molecular mechanisms behind these cellular responses have yet to be elucidated. We employed the human cervical cancer cell line CaSki as a cellular model and examined the effect of cell apoptosis and proliferation under gradient thermal conditions (43, 45 and 47˚C for 40 min). Heat treatment was found to induce CaSki cell apoptosis and necrosis. Cell cycle analysis showed that cells were arrested in S phase upon the application of hyperthermia, and MTT analysis revealed that cell viability was also reduced. Of the thermal conditions, 45˚C exhibited the best induction of apoptosis, while 47˚C induced direct fierce necrosis. This was further demonstrated by examining the expression level of several key apoptosis-related genes: caspase-3, Smac and Survivin. During apoptosis, caspase-3 and Smac levels were up-regulated, whereas anti-apoptotic Survivin was down-regulated, enhancing programmed cell death. Our results reveal that heating at ≥45˚C induced cell apoptosis and necrosis, and inhibited cell proliferation at both the cellular and molecular levels. These findings support the use of hyperthermia in a clinical setting for the treatment of human cervical cancer.
Molecular Medicine Reports 01/2011; 4(1):187-91. · 1.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel bioconjugation of amino saline capped Fe3O4 magnetic nanoparticles (MNPs) with bovine serum albumin (BSA) was developed by applying glutaraldehyde as activator. Briefly, Fe3O4 MNs were synthesized by the chemical co-precipitation method. Surface modification of the prepared MNPs was performed by employing amino saline as the coating agent. Glutaraldehyde was further applied as an activation agent through which BSA was conjugated to the amino-coated MNPs. The structure of the BSA-MNs was confirmed by FTIR analysis. Physico-chemical characterizations of the BSA-MNPs, such as surface morphology, surface charge and magnetic properties were investigated by Transmission Electron Microscopy (TEM), zeta-Potential and Vibrating Sample Magnetometer (VSM), etc. Magnetic inductive heating characteristics of the BSA-MNPs were analyzed by exposing the MNPs suspension (magnetic fluid) under alternative magnetic field (AMF). The results demonstrate that BSA was successfully conjugated with amino-coated MNs mediated through glutaraldehyde activation. The nanoparticles were spherical shaped with approximately 10 nm diameter. Possessing ideal magnetic inductive heating characteristics, which can generate very rapid and efficient heating while upon AMF exposure, BSA-MNPs can be applied as a novel candidature for magnetic nanothermotherapy for cancer treatment. In vitro cytotoxicity study on the human hepatocellular liver carcinoma cells (HepG-2) indicates that BSA-MNP is an efficient agent for cancer nanothermotherapy with satisfied biocompatibility, as rare cytotoxicity was observed in the absence of AMF. Moreover, our investigation provides a methodology for fabrication protein conjugated MNPs, for instance monoclonal antibody conjugated MNPs for targeting cancer nanothermotherapy.
Journal of Nanoscience and Nanotechnology 11/2010; 10(11):7117-20. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we proposed carbonyl iron powder (CIP) as a novel mediator for arterial embolization hyperthermia (AEH). In
vitro cytotoxicity study with cultured L929 cells was carried out to test the biocompatibility of the CIP. Effect of alternative
magnetic field (AMF) on the temperature rise of CIP was performed by exposing the CIP/Lipiodol suspensions under AMF with
different field strength. In vivo heating curve of the hepatic artery after transcatheter arterial embolization (TAE) was
also conducted by applying New Zealand half lop rabbits as animal model. Cytotoxicity study demonstrated that CIP showed good
biocompatibility. Heating curves, both in vitro and in vivo, revealed that CIP possessed ideal property of inductive heating
characteristics under AMF. Our findings suggest that CIP is a very promising mediator candidature of AEH for clinical application.
KeywordsMagnetic Inductive Hyperthermia–Arterial Embolization Hyperthermia–Carbonyl Iron Powder–Heating–Cancer Targeted Treatment
[Show abstract][Hide abstract] ABSTRACT: Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) can play crucial roles for medical applications such as cancer magnetic induction hyperthermia, magnetic resonance imaging and magnetofection. Herein we report the results of modified magnetic nanoparticles coated with protamine peptides containing nuclear localization signal sequences. Functionalization of these SPIONs under alternating magnetic field radiation resulted in more cellular uptake and higher-efficient cytotoxicity in HepG2 cells. The work demonstrates that functionalized SPIONs can be used as a novel kind of highly efficient magnetic mediator for magnetic induction intracellular hyperthermia.
[Show abstract][Hide abstract] ABSTRACT: Amphipathic polymer pullulan acetate (PA)-coated magnetic nanoparticles were prepared and characterized by various physicochemical
means. The cytotoxicity and cellular uptake of the magnetic nanoparticles were examined. The hyperthermic effect of the magnetic
nanoparticles on tumor cells was evaluated. Transmission electron microscopy (TEM) showed that the PA coated magnetic nanoparticles
(PAMNs) had spherical morphology. Dynamic light scattering (DLS) showed that the size distribution of PAMNs was unimodal,with
an average diameter of 25.8 nm ± 6.1 nm. The presence of the adsorbed layer of PA on the magnetite surface was confirmed by
Fourier transform infrared (FTIR) spectroscopy. Magnetic measurements revealed that the saturation magnetization of the PAMNs
reached 51.9 emu/g and the nanoparticles were superparamagnetic. Thermogravimetric analysis (TGA) showed that the Fe3O4 particles constituted 75 wt% of the PAMNs. The PAMNs had good heating properties in an alternating magnetic field. Cytotoxicity
assay showed that PAMNs exhibited no significant cytotoxicity against L929 cells. TEM results showed that a large number of
PAMNs were internalized into KB cells. PAMNs have good hyperthermia effect on KB cells in vitro by magnetic field induced hyperthermia. These novel magnetic nanoparticles have great potential as magnetic hyperthermia
Nano Research 01/2010; 3(1):23-31. · 7.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An effective treatment method for acnes is meaningful for both doctors and patients. This paper demonstrated a new concept of acne treatment based on Bio-heat Transfer Theory. An alternative heating treatment system is developed to control the contact heating degree in a precise way. The preliminary biomedical experiments were performed, and further experiments-under more strict condition are still ongoing expecting clear evidence for pre-clinical trials.
[Show abstract][Hide abstract] ABSTRACT: Cancer comprehensive treatment has been fully acknowledged as it can provide an effective multimodality approach for fighting cancers. In this study, various innovative technologies for cancer treatment including cancer nanotechnology, chemotherapy by sustainable release, as well as magnetic induction hyperthermia (MIH) have been integrated for the purpose of cancer comprehensive treatment. Briefly, such kind of treatment can be realized by applying of the tailored magnetic nanoparticles (MNPs) composite polymeric film. Fe3O4 MNPs acting as the agent for MIH, and anti-cancer drug docetaxel as chemotherapeutic agent were incorporated within the biodegradable polymeric film. Physiochemical characterizations on MNPs and the film have been systematically carried out by various instrumental analyses. Our results demonstrated that the film has been successfully fabricated by the solvent cast method. Hyperthermia could be induced by stimulating the nanocomposite film under an alternative magnetic field (AMF). The incorporation of MNPs, as well as hyperthermia would facilitate the drug release from the polymeric film. The in-vitro cytotoxicity results indicated the bi-modal cancer treatment approach for combined MIH and chemotherapy is more effective than the mono-modal treatment by docetaxel treatment. The magnetic nanocomposite film can realize cancer comprehensive treatment thus has great potential in clinical application.
[Show abstract][Hide abstract] ABSTRACT: Hyperthermia by heating in-stent is a potentially new method to treat esophageal cancer. This study assessed the safety of heating the rabbit esophagus with a nitinol stent in an alternating magnetic field (AMF) and investigated whether this method offers a therapeutic option for esophageal cancer. Nitinol stents were placed in the cervical esophagi of healthy rabbits, which were heated in an AMF for different times at 43, 46 and 50°C. The esophagi were histologically examined after a week to observe whether there was transmural necroses. Then esophageal cancer of rabbit placed nitinol stents were heated in an AMF at 46°C for 10min. Stents were heated to a target temperature within 5min. The highest tolerated temperature and time for the healthy rabbit esophagus was at 46°C for 10min. Tumor growth was delayed by heating and it was statistically significant. Heating the rabbit esophageal wall at 46°C for 10min proves to be safe and effective in delaying tumor growth.
Progress in Natural Science - PROG NAT SCI. 01/2009; 19(12):1713-1719.
[Show abstract][Hide abstract] ABSTRACT: To determine whether conventional hyperthermia (42–45°C) or ablation therapy (>50°C) achieves better synergistic effects on direct cytotoxicity and anti-tumor immunity, we compared the therapeutic effects of two hyperthermia temperatures, 43 and 55°C, in terms of cytotoxicity and upregulation of immune functions in a mouse malignant melanoma model. Melanoma-bearing mice were treated by directly applying regional hyperthermia to the tumor nodule with a heating light at a temperature of 43°C for 30min or 55°C for 10min. The tumor growth curve and mice survival rate were observed. To investigate the hyperthermia-induced immunological response, peripheral blood CD4+ and CD8+ T cells and the serum IL-2 level were determined. Our results indicated that application of regional hyperthermia at the ablation temperature (such as 55°C) achieved better synergistic anti-tumor effects than did conventional hyperthermia (43°C). Significant increases in the number of peripheral blood CD4+ T cells and the serum IL-2 level likely contributed to the underlying mechanism.
Progress in Natural Science - PROG NAT SCI. 01/2009; 19(12):1699-1704.
[Show abstract][Hide abstract] ABSTRACT: Hyperthermia induced by magnetic nanoparticles is a recent therapeutic approach for local targeting of hyperthermia and thermoab-lation and is a promising treatment of malignant tumors. The purpose of this study is to evaluate the potential and therapeutic effect of magnetic fluid hyperthermia on the rabbit VX2 liver tumor model. Rabbits bearing liver tumors 14 days after tumor implantation were randomly divided into five groups of 10 cases each, including three control groups and two hyperthermia groups. Hyperthermia was carried out immediately after a single intratumoral injection of uncoated water-based Fe 3 O 4 magnetic fluid under an alternating magnetic field only once as one hyperthermia group and repeated hyperthermia after 5 days as the other treated group. The distribution of mag-netic fluid was evaluated by CT scanning. All animals were sacrificed 4 weeks after tumor implantation. The therapeutic effect was deter-mined by tumor size and macroscopic and pathological examination of the liver tumor. The local higher density imaging of intratumoral magnetic fluid deposits compared to the surrounding tissue was clearly observed by CT scanning. Twenty-eight days after tumor implan-tation, the tumor maximal diameter and tumor volume of two hyperthermia were both significantly less than those of control groups (P < 0.05). Tumor volume inhibition by single or repeated hyperthermia compared to the three control groups was 71.93–79.91% and 92.34–94.46% (P < 0.05), respectively. Under a microscope, coagulation necrosis was observed in the heated area, which had a clear boundary line with the surrounding tissue. The intratumoral distribution of magnetic nanoparticles, especially in the area of necrosis, appeared much more homogenous than in the untreated ones. This study demonstrates that hyperthermia induced by direct intratumoral injection of magnetic fluid can be used safely, and a well-homogenized distribution of high intratumoral temperature without heating adjacent to normal tissue can be achieved.
Progress in Natural Science - PROG NAT SCI. 01/2009; 19(12).