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载铁液固相变型PLGA植入物原位磁感应热消融裸鼠SKOV3人卵巢癌
Fe-loaded liquid-solid phase inversion PLGA implantation for magnetic hyperthermal ablation of SKOV3 human ovarian cancer in situ of nude mice
【摘要】 目的制备载铁的液固相变型聚乳酸-羟基乙酸(PLGA)原位植入物(Fe-ISFIs),观察其在超高频交变磁场下对裸鼠SKOV3人卵巢癌的消融效果。方法制备含铁质量分数40%的Fe-ISFIs,测定不同量(50、25μl)Fe-ISFIs相变后在交变磁场中5min内温度的变化,然后注入不同量(50、25μl)Fe-ISFIs于离体牛肝中,置于交变磁场中不同时间(1、2、3、5min),观察牛肝消融直径,并选取最佳治疗方案。取9只荷SKOV3人卵巢癌裸鼠,于超声引导下向瘤内局部注射50μl Fe-ISFIs,之后分为2组:第1组6只裸鼠于交变磁场中照射3min,第2组3只裸鼠不进行磁性照射。治疗完成后第1组中任选3只、第2组选1只裸鼠处死,并取下肿瘤行HE及TTC染色,每日肉眼观察其余裸鼠肿瘤生长情况。结果体外加热实验结果显示,遇水发生液固相变后的Fe-ISFIs在交变磁场中温度逐渐增高,50μl Fe-ISFIs较25μl Fe-ISFIs加热效果显著;牛肝消融实验观察到50μl Fe-ISFIs在3min内消融直径可达(1.18±0.18)cm,而25μl Fe-ISFIs加热效果较差,5min内消融直径只有(0.94±0.10)cm;TTC染色结果显示经交变磁场照射治疗后部分肿瘤消融完全,但仍存在消融不全的肿瘤。HE染色见肿瘤组织坏死征象,肿瘤细胞出现核固缩或消失;肉眼观察第1组中肿瘤于治疗后第2天肿瘤组织开始脱落、结痂,约14天创面逐渐愈合,肿瘤组织消失(完全消融的肿瘤);第2组中肿瘤随时间而逐渐增大。结论 Fe-ISFIs结合超高频交变磁场能够在较短时间内有效消融裸鼠SKOV3人卵巢癌。
【Abstract】 Objective To prepare Fe-loaded liquid-solid phase inversion poly(lactic-co-glycolic acid,PLGA)implants(Fe-ISFIs),and to observe the ablation efficiency on SKOV3human ovarian cancer.Methods 40wt-%filler fractions of Fe in the Fe-ISFIs were prepared.Temperature changes of solid Fe-ISFIs(50μl,25μl,respectively)in alternating magnetic field within 5min were observed.Then 50μl and 25μl of Fe-ISFIs were injected into the isolated bovine liver tissue, and alternating magnetic field was applied for 1,2,3,5min,respectively.The diameters of the ablated liver tissue were recorded,and optimal treatment regimen was chosen for further in vivo experiment.50μl Fe-ISFIs were directly injected into the tumors of 9nude mice bearing SKOV3human ovarian cancer,and the mice were then divided into two groups: Group 1for treatment in alternating magnetic field for 3min,group 2without magnetic field.Later,3nude mice of group 1and 1of group 2were euthanized,and the tumors were resected for TTC and HE staining.The remaining nude mice were observed for tumor growth.Results The heating experiment in vitro showed that the temperature of Fe-ISFIs increased with time,and 50μl of Fe-ISFIs was better.In the isolated bovine liver tissue,50μl of Fe-ISFIs got(1.18±0.18)cm of ablated diameter in 3min,while that of 25μl only got(0.94±0.10)cm in 5min.TTC staining of tumor tissue showed parts of nude mice’tumor were completely ablated,while still existed incomplete ablated tumors.HE staining demonstrated the coagulation,which showed cells with pyknotic nuclei or an absence of nuclei.In the observation of tumor growth,the tumors of group 2grew well with time,while in group 1,the ablated tumors fell off at the 2nd day after treatment and then gradually healed at about 14days after treatment.Conclusion Fe-ISFIs combined with alternating magnetic field are able to ablate SKOV3human ovarian cancer in short time.
【Key words】 Magnetic hyperthermia; Implants,experimental; Phase transition; Ovarian neoplasms;
- 【文献出处】 中国介入影像与治疗学 ,Chinese Journal of Interventional Imaging and Therapy , 编辑部邮箱 ,2013年11期
- 【分类号】R737.31
- 【被引频次】1
- 【下载频次】76