摘要
目的:考察透明质酸(HA)修饰的中空介孔硫化铜纳米粒(HMCuS NPs)负载阿霉素(DOX)载药体系在乳腺癌模型裸鼠体内的分布行为及药效学特征。方法:荷MCF-7人乳腺癌裸鼠移植模型建立后,尾静脉注射药物后,通过活体成像系统实时考察HMCuS和HMCuS-HA载体系统对IR783体内分布的影响。另取60只荷瘤裸鼠随机分为10组,每组6只:生理盐水组、生理盐水+近红外光(NIR)组、HMCuS-HA组、HMCuS-HA+NIR组、DOX组、DOX+NIR组、DOX/HMCuS组、DOX/HMCuS+NIR组、DOX/HMCuS-HA组、DOX/HMCuS-HA+NIR组。采取尾静脉注射方式给药,每2 d给药1次,共给药6次。激光组在给药8 h后使用808 nm激光照射肿瘤部位(2 W/cm2,3min)。以相对瘤体积、抑瘤率、肿瘤组织的HE染色等考察载药系统在NIR照射下的抗肿瘤活性;通过监测裸鼠生存状态、体重变化、正常组织的病理检查等评价载药系统的生物安全性。结果:HMCuS-HA载体系统增强了在肿瘤部位的蓄积,DOX/HMCuS-HA+NIR组抑瘤率高达(88. 87±6. 14)%; HE染色后发现肿瘤组织出现大范围凋亡和坏死情况;体内安全性评估结果表明HMCuS-HA载体具有良好的生物安全性,DOX/HMCuS-HA靶向制剂可以降低DOX的心脏毒性。结论:DOX/HMCuS-HA具有优异的肿瘤靶向性,实现了肿瘤靶向的光热治疗与化疗的协同治疗,具有明显的抗肿瘤效果。
Aim: To investigate biodistribution and pharmacodynamics of hyaluronic acid( HA) -modified doxorubicin ( DOX) -loaded hollow mesoporous copper sulfide nanoparticles ( HMCuS NPs) in MCF-7 tumor bearing mice. Methods: The in vivo behavior of HMCuS and HMCuS-HA was investigated by using the noninvasive optical imaging system. For the in vivo antitumor experiments,the MCF-7 tumor-bearing mice were allocated into ten groups( six mice per group) . The mice were administered with normal saline,normal saline + NIR laser,HMCuS-HA,HMCuS-HA + NIR laser,DOX, DOX + NIR laser,DOX/HMCuS,DOX/HMCuS + NIR laser,DOX/HMCuS-HA,DOX/HMCuS-HA + NIR laser. The different formulations were administrated through tail vein injection every 2 days for 6 times,respectively. The laser-treated groups were exposed to an 808 nm laser at a power density of 2 W/cm2 for 3 min at 8 h after injection. And the anti-tumor effect of DOX/HMCuS-HA under NIR irradiation was evaluated by the relative tumor volume,the inhibition rate and the histological examination. In addition,the toxicity of the above formulations was determined by monitoring animal behavior and the weight loss. When the treatment finished,tissues were removed for histological examination. Results: The HMCuSHA NPs preferentially accumulated at the tumor site. The inhibition rate of the tumor in mice treated with DOX/HMCuS-HA under NIR irradiation was ( 88. 87 ± 6. 14) %. HE staining exhibited a large amount of cell apoptosis and necrosis. Additionally, HMCuS-HA exhibited good biosafety,and reduced toxic side effects of DOX on the heart to a certain extent. Conclusion: The DOX/HMCuS-HA drug delivery system possesses the excellent tumor targeting ability,and could realize the synergistic combination of chemophotothermal therapy,which shows a substantial therapeutic effect.
作者
贾欣
冯倩华
张超锋
王蕾
王希
杜娟
JIA Xin;FENG Qianhua;ZHANG Chaofeng;WANG Lei;WANG Xi;DU Juan(School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou450001)
出处
《郑州大学学报（医学版）》
CAS
北大核心
2018年第6期738-743,共6页
Journal of Zhengzhou University(Medical Sciences)
基金
国家自然科学基金资助项目(81202485
81273451)
关键词
阿霉素
硫化铜
透明质酸
体内分布
药效学
doxorubicin
copper sulfide
hyaluronic acid
biodistribution
pharmacodynamics
