肿瘤磁纳米热疗用交变磁场发生仪器实验样机的研制与Fe_3O_4纳米磁流体磁热效应研究
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摘要
本课题主要研制肿瘤磁纳米热疗用交变磁场发生仪器的实验样机,并在此实验平台上开展Fe_3O_4纳米磁流体磁热效应研究。
肿瘤磁纳米热疗是特异向体内肿瘤局部导向输注具有铁磁特性的磁性纳米粒,磁性纳米粒靶向识别肿瘤组织并定位于肿瘤病灶,在外部交变磁场作用下释放能量发热,使肿瘤病灶形成升温区和磁场辐射密集区,避免周边正常组织升温和减少辐射,达到短时杀伤肿瘤细胞,打击潜在转移和亚临床病灶。
本课题研究和综合了大量肿瘤磁纳米热疗的文献资料。通过对高频磁场理论的分析和计算,参考电磁感应加热的设计范例,提出了应用于肿瘤磁纳米热疗的特殊高频磁场装置设计方案,并研制出肿瘤磁纳米热疗用交变磁场发生仪器实验样机。
采用共沉淀法制备了用于肿瘤磁纳米热疗的PEG-PEI/Fe_3O_4纳米磁流体,并对磁流体进行粒径和Zeta电位测定,X射线衍射、红外扫描、振动样品磁强分析,结果表明PEG-PEI/Fe_3O_4纳米磁流体适于肿瘤磁纳米热疗。
在研制的肿瘤磁纳米热疗用交变磁场发生仪器实验样机上对Fe_3O_4纳米磁流体进行磁热效应研究,同时对肿瘤磁纳米热疗用交变磁场发生仪器实验样机的性能参数进行了初步评估。建立了纳米磁流体磁热效应数学模型,很好地描述纳米磁流体在交变磁场中温度与磁场强度、升温时间的相关关系。
肿瘤磁纳米热疗用交变磁场发生仪器实验样机的研制为国内在纳米磁性材料结合磁场加热治疗肿瘤的设备开发方面提供新方法。表明纳米磁性材料应用于肿瘤热疗的方法具有可行性。这些工作对以后磁场装置的设计、动物实验和临床试验的设计,进一步的临床治疗设备的开发都有指导意义,同时也将为纳米磁性材料的有关应用研究提供设备平台和理论基础。
The aim of this research subject was to develop experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles, and researched magnetocaloric effect of Fe_3O_4 nano-magnetic liquid.
Hyperthermia treatment of tumors with magnetic nanoparticles was that injected magnetic nanoparticles into tumors, then magnetic nanoparticles targeted tumor focal lesions. Magnetic nanoparticles released energy under alternating magnetic field, the temperature of tumor focal lesions would rise, and normal tissues would not damage. It could damage tumor cells and subclinical tumor focal lesions.
After researched lots of documents about hyperthermia treatment of tumors with magnetic nanoparticles, analyzed and calculated the high frequency magnetic field theory, referred to design method of induction heating, then put forward design method of high frequency magnetic field generator device for hyperthermia treatment of tumors with magnetic nanoparticles, and developed experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles.
PEG-PEI/Fe_3O_4 nano-magnetic liquid was prepared for hyperthermia treatment of tumors with magnetic nanoparticles by coprecipitation method, and mensurated particle size, Zeta electric potential, X-ray diffraction pattern, IR spectra, magnetization. The results showed that PEG-PEI/Fe_3O_4 nano-magnetic liquid fit for hyperthermia treatment of tumors with magnetic nanoparticles.
The magnetocaloric effect of Fe_3O_4 nano-magnetic liquid was researched by experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles, and evaluated the parameters of the device. The mathematic model of magnetocaloric effect of nano-magnetic liquid was build. The mathematic model described the relations between the temperature of nano-magnetic liquid under alternating magnetic field, magnetic field intensity and time.
Development of experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles put forward new method for device development of hyperthermia treatment of tumors with alternating magnetic field. It showed that hyperthermia treatment of tumors with magnetic nanoparticles was feasible. The works had guidance significance of device design, animal experiments, clinical trial and clinical equipment development. It also provided equipment platform and theoretical foundation for application researches of magnetic nanoparticle.
肿瘤磁纳米热疗是特异向体内肿瘤局部导向输注具有铁磁特性的磁性纳米粒,磁性纳米粒靶向识别肿瘤组织并定位于肿瘤病灶,在外部交变磁场作用下释放能量发热,使肿瘤病灶形成升温区和磁场辐射密集区,避免周边正常组织升温和减少辐射,达到短时杀伤肿瘤细胞,打击潜在转移和亚临床病灶。
本课题研究和综合了大量肿瘤磁纳米热疗的文献资料。通过对高频磁场理论的分析和计算,参考电磁感应加热的设计范例,提出了应用于肿瘤磁纳米热疗的特殊高频磁场装置设计方案,并研制出肿瘤磁纳米热疗用交变磁场发生仪器实验样机。
采用共沉淀法制备了用于肿瘤磁纳米热疗的PEG-PEI/Fe_3O_4纳米磁流体,并对磁流体进行粒径和Zeta电位测定,X射线衍射、红外扫描、振动样品磁强分析,结果表明PEG-PEI/Fe_3O_4纳米磁流体适于肿瘤磁纳米热疗。
在研制的肿瘤磁纳米热疗用交变磁场发生仪器实验样机上对Fe_3O_4纳米磁流体进行磁热效应研究,同时对肿瘤磁纳米热疗用交变磁场发生仪器实验样机的性能参数进行了初步评估。建立了纳米磁流体磁热效应数学模型,很好地描述纳米磁流体在交变磁场中温度与磁场强度、升温时间的相关关系。
肿瘤磁纳米热疗用交变磁场发生仪器实验样机的研制为国内在纳米磁性材料结合磁场加热治疗肿瘤的设备开发方面提供新方法。表明纳米磁性材料应用于肿瘤热疗的方法具有可行性。这些工作对以后磁场装置的设计、动物实验和临床试验的设计,进一步的临床治疗设备的开发都有指导意义,同时也将为纳米磁性材料的有关应用研究提供设备平台和理论基础。
The aim of this research subject was to develop experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles, and researched magnetocaloric effect of Fe_3O_4 nano-magnetic liquid.
Hyperthermia treatment of tumors with magnetic nanoparticles was that injected magnetic nanoparticles into tumors, then magnetic nanoparticles targeted tumor focal lesions. Magnetic nanoparticles released energy under alternating magnetic field, the temperature of tumor focal lesions would rise, and normal tissues would not damage. It could damage tumor cells and subclinical tumor focal lesions.
After researched lots of documents about hyperthermia treatment of tumors with magnetic nanoparticles, analyzed and calculated the high frequency magnetic field theory, referred to design method of induction heating, then put forward design method of high frequency magnetic field generator device for hyperthermia treatment of tumors with magnetic nanoparticles, and developed experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles.
PEG-PEI/Fe_3O_4 nano-magnetic liquid was prepared for hyperthermia treatment of tumors with magnetic nanoparticles by coprecipitation method, and mensurated particle size, Zeta electric potential, X-ray diffraction pattern, IR spectra, magnetization. The results showed that PEG-PEI/Fe_3O_4 nano-magnetic liquid fit for hyperthermia treatment of tumors with magnetic nanoparticles.
The magnetocaloric effect of Fe_3O_4 nano-magnetic liquid was researched by experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles, and evaluated the parameters of the device. The mathematic model of magnetocaloric effect of nano-magnetic liquid was build. The mathematic model described the relations between the temperature of nano-magnetic liquid under alternating magnetic field, magnetic field intensity and time.
Development of experimental prototype of alternating magnetic field generator for hyperthermia treatment of tumors with magnetic nanoparticles put forward new method for device development of hyperthermia treatment of tumors with alternating magnetic field. It showed that hyperthermia treatment of tumors with magnetic nanoparticles was feasible. The works had guidance significance of device design, animal experiments, clinical trial and clinical equipment development. It also provided equipment platform and theoretical foundation for application researches of magnetic nanoparticle.
引文
[1]ASHEWELL G,HARFORD J.Carbohydrate -specific receptors of the liver[J].Annu Rew Biochem,1982,51:531-554.
[2]张阳德.纳米生物技术学[M].北京:科学出版社,2005:107.
[3]张阳德,李浩.纳米载体肝靶向纳米药物研究进展[J].中国医学工程杂志,2002,11(6):75-77.
[4]GILCHRIST R K,MEDAL R,SHOREY W D,et al.Selective inductive heating of lymph nodes[J].Annals of Oncology,1957,146(4):595-606.
[5]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制[J].中国现代医学杂志,2001,11(3):2-3.
[6]ADLER R,HURWITZ E,WANDS J R,et al.Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrabepatic tumor in athymic mice[J].Hepatology,1995,22(5):1482-1487.
[7]HERGT R,W.ANDRAE.Physical limits of hyperthermia using magnetite fine particles[J].IEEE Transactions on magnetics,34(5):3745-3754.
[8]PANKHURST Q A,CONNOLLY J,JONES S K,et al.Application of magnetic nanoparticles in biomedicine[J].Journal of physics D:Applied Physics,2003,36:R167-R181.
[9]田民波.磁性材料[M].北京:清华大学出版社,2001,351-361.
[10]MOROZ P,JONES S K,WINTER J,et al.Targeting liver tumors with hyperthermia:Ferromagnetic embolization in a rabbit liver tumor model[J].Journal of Surgical Oncology,2001,78(1):22-29.
[11]何跃明.恶性肿瘤的磁靶向热疗[J].国外医学·物理医学与康复学分,2003,23(2):96-100.
[12]KOTTE A N T J,WIERINGEN N V,LAGENDJKk J J W.Modelling tissue heating with ferromagnetic seed[J].Physics in medicine and Biology,1998,43:105-120.
[13]JORDANA,WUST P,SCHOLZ R,et al.Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetics fields in vitro[J].International Journal of Hyperthermia,1996,12(6):705-722.
[14]MOROZ P,JONES S K,GRAY B N,et al.Magnetic medical hyperthermia:current status and future direction[J].Int J Hyperthermia,2002,18(4):267-284.
[15]ATKINSON W J,BREZOVlCH I A,CHAKRABOTY D P.Usable frequencies in hyperthermia with thermal seeds[J].IEEE Transactions on Biomedical Engineering,1984,31(1):70-75.
[16]STAUFFER P R,SNEED P K,HASHEMI H,et al.Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants[J].IEEE Transactions on Biomedical Engineering,1994,41(1):17-28.
[17]夏启胜,刘轩,徐波,等.铁磁热籽加温治疗肿瘤机制研究现状[J].中国医学物理学杂志,2004,21(4):213-215.
[18]BERTHUSEN A H,TUCHER R D,PARK J B.A field -focusing device to increase power output of thermoRod trade mark implants for thermal ablation of tissue[J].J Biomed Mater Res,2002,63(5):650-656.
[19]MASASHIGE SHINKAI.Intracellular hyperthermia for cancer using magnetic cationic liposomes[J].Journal of Magnetism and Magnetic Material,1999,194:176-184.
[20]MOROZ P,JONES S K,GRAY B N,et al.Tumor response to arterial embolization hyperthermia and direct injection hyperthermia in a rabbit liver tumor model[J]Journal of Surgical Oncology 2002,80(3):149-156.
[21]MOROZ P,JONES S K,GRAY B N,et al.The effect of tumor size on ferromagnetic embolization hyperthermia in arabbit tumour model[J].International Journal of Hyperthermia,2002,18(2):129-140.
[22]MINAMIMURA T,SATO H,KASAOKN S,et al.Tumor regression by inductive hyperthermia combined with hepatic embolization using dextran magnetite incorporated microspheres in rats[J].International Journal of Oncology,2000,16(6):1153-1158.
[23]ANDRESS JORDAN.Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia[J].Journal of Magnetism and Magnetic Materials,2001,225:118-126.
[24]何跃明,吕新生,艾中立,等.磁介导热疗联合顺铂化疗对肝癌细胞的影响及其机制[J].中华实验外科杂志,2004,21(10):1170-1172.
[25]MINGMA.Preparation and characterization of magnetite nanoparticles coated by amino silane[J].Colliods and Surface A:physicochem.Eng.Aspects,2003,212(2-3):219-226.
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[1]GILCHRIST R K,MEDAL R,SHOREY W D,et al.Selective inductive heating of lymph nodes[J].Annals of Oncology,1957,146(4):595-606.
[2]张阳德.纳米生物技术学[M].北京:科学出版社,2005:107.
[3]张阳德,李浩.纳米载体肝靶向纳米药物研究进展[J].中国医学工程杂志,2002,11(6):75-77.
[4]ASHEWELL G,HARFORD J.Carbohydrate -specific receptors of the liver[J].Annu Rew Biochem,1982,51:531-554.
[5]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制[J].中国现代医学杂志,2001,11(3):2-3.
[6]ADLER R,HURWITZ E,WANDS J R,et al.Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrabepatic tumor in athymic mice[J].Hepatology,1995,22(5):1482-1487.
[7]HERGT R,W.ANDRAE.Physical limits of hyperthermia using magnetite fine particles[J].IEEE Transactions on Magnetics,34(5):3745-3754.
[8]PANKHURST Q A,CONNOLLY J,JONES S K,et al.Application of magnetic nanoparticles in biomedicine[J].Journal of physics O:Applied Physics,2003,36:R167-R181.
[9]田民波.磁性材料[M].北京:清华大学出版社,2001,351-361.
[10]MOROZ P,JONES S K,WINTER J,et al.Targeting liver tumors with hyperthermia:Ferromagnetic embolization in a rabbit liver tumor model[J].Journal of Surgical Oncology,2001,78(1):22-29.
[11]何跃明.恶性肿瘤的磁靶向热疗[J].国外医学·物理医学与康复学分,2003,23(2):96-100.
[12]KOTTE A N T J,WIERINGEN N V,LAGENDJKk J J W.Modelling tissue heating with ferromagnetic seed[J].Physics in Medicine and Biology,1998,43:105-120.
[13]JORDANA,WUST P,SCHOLZ R,et al.Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetics fields in vitro[J].International Journal of Hyperthermia,1996,12(6):705-722.
[14]MOROZ P,JONES S K,GRAY B N,et al.Magnetic medical hyperthermia:current status and future direction[J].Int J Hyperthermia,2002,18(4):267-284.
[15]ATKINSON W J,BREZOVICH I A,CHAKRABOTY D P.Usable frequencies in hyperthermia with thermal seeds[J].IEEE Transactions on Biomedical Engineering,1984,31(1):70-75.
[16]STAUFFER P R,SNEED P K,HASHEMI H,et al.Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants[J].IEEE Transactions on Biomedical Engineering,1994,41(1):17-28.
[17]夏启胜,刘轩,徐波,等.铁磁热籽加温治疗肿瘤机制研究现状[J].中国医学物理学杂志,2004,21(4):213-215.
[18]BERTHUSEN A H,TUCHER R D,PARK J B.A field -focusing device to increase power output of thermoRod trade mark implants for thermal ablation of tissue[J].J Biomed Mater Res,2002,63(5):650-656.
[19]MASASMIGE SHINKAI.Intracellular hyperthermia for cancer using magnetic cationic liposomes[J].Journal of Magnetism and Magnetic Material,1999,194:176-184.
[20]MOROZ P,JONES S K,GRAY B N,et al.Tumor response to arterial embolization hyperthermia and direct injection hyperthermia in a rabbit liver tumor model[J]Journal of Surgical Oncology 2002,80(3):149-156.
[21]MOROZ P,JONES S K,GRAY B N,et al.The effect of tumor size on ferromagnetic embolization hyperthermia in arabbit tumour model[J].International Journal of Hyperthermia,2002,18(2):129-140.
[22]MINAMIMURAT,SATO H,KASAOKNS,et al.Tumor regression by inductive hyperthermia combined with hepatic embolization using dextran magnetite incorporated microspheres in rats[J].International Journal of Oncology,2000,16(6):1153-1158.
[23]ANDRESS JORDAN.Presentation of a new magnetic field therapy system for the treatment of human solid tumors with magnetic fluid hyperthermia[J].Journal of Magnetism and Magnetic Materials,2001,225:118-126.
[24]何跃明,吕新生,艾中立,等.磁介导热疗联合顺铂化疗对肝癌细胞的影响及其机制[J].中华实验外科杂志,2004,21(10):1170-1172.
[25]马明.四氧化三铁纳米粒子与癌细胞的相互作用的初步研究[J].东南大学学报,2003,33(2):203-207.
[26]吴亚,孙剑飞,郭全忠,等.肿瘤热疗用交变磁场发生器的研制[J]东南大学学报(自然科学版),2004,34(6):794-796.
[27]MING MA.Preparation and characterization of magnetite nanoparticles coated by amino silane[J].Colliods and Surface A:physicochem.Eng.Aspects,2003,212(2-3):219-226.
[2]张阳德.纳米生物技术学[M].北京:科学出版社,2005:107.
[3]张阳德,李浩.纳米载体肝靶向纳米药物研究进展[J].中国医学工程杂志,2002,11(6):75-77.
[4]GILCHRIST R K,MEDAL R,SHOREY W D,et al.Selective inductive heating of lymph nodes[J].Annals of Oncology,1957,146(4):595-606.
[5]张阳德,龚连生.磁性阿霉素白蛋白纳米粒的研制[J].中国现代医学杂志,2001,11(3):2-3.
[6]ADLER R,HURWITZ E,WANDS J R,et al.Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrabepatic tumor in athymic mice[J].Hepatology,1995,22(5):1482-1487.
[7]HERGT R,W.ANDRAE.Physical limits of hyperthermia using magnetite fine particles[J].IEEE Transactions on magnetics,34(5):3745-3754.
[8]PANKHURST Q A,CONNOLLY J,JONES S K,et al.Application of magnetic nanoparticles in biomedicine[J].Journal of physics D:Applied Physics,2003,36:R167-R181.
[9]田民波.磁性材料[M].北京:清华大学出版社,2001,351-361.
[10]MOROZ P,JONES S K,WINTER J,et al.Targeting liver tumors with hyperthermia:Ferromagnetic embolization in a rabbit liver tumor model[J].Journal of Surgical Oncology,2001,78(1):22-29.
[11]何跃明.恶性肿瘤的磁靶向热疗[J].国外医学·物理医学与康复学分,2003,23(2):96-100.
[12]KOTTE A N T J,WIERINGEN N V,LAGENDJKk J J W.Modelling tissue heating with ferromagnetic seed[J].Physics in medicine and Biology,1998,43:105-120.
[13]JORDANA,WUST P,SCHOLZ R,et al.Cellular uptake of magnetic fluid particles and their effects on human adenocarcinoma cells exposed to AC magnetics fields in vitro[J].International Journal of Hyperthermia,1996,12(6):705-722.
[14]MOROZ P,JONES S K,GRAY B N,et al.Magnetic medical hyperthermia:current status and future direction[J].Int J Hyperthermia,2002,18(4):267-284.
[15]ATKINSON W J,BREZOVlCH I A,CHAKRABOTY D P.Usable frequencies in hyperthermia with thermal seeds[J].IEEE Transactions on Biomedical Engineering,1984,31(1):70-75.
[16]STAUFFER P R,SNEED P K,HASHEMI H,et al.Practical induction heating coil designs for clinical hyperthermia with ferromagnetic implants[J].IEEE Transactions on Biomedical Engineering,1994,41(1):17-28.
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