纳米化贝伐单抗通过抗血管新生抑制骨肉瘤的增殖和迁移  

Nanosized bevacizumab inhibits the proliferation and migration of osteosarcoma through anti-neovascularization

作　　者：邓爱露 袁发 廖庆 徐翰 王一桦 罗栩伟 周春阳[1] DENG Ailu;YUAN Fa;LIAO Qing;XU Han;WANG Yihua;LUO Xuwei;ZHOU Chunyang(Institute of Materia Medica,North Sichuan Medical College,Nanchong 620000,China;Bone and Joint Disease Center,Nanchong Central Hospital,Nanchong 637100,China;Southwest Medical University Zigong Affiliated Hospital/Zigong Mental Health Center,Zigong 643020,China)

机构地区：[1]四川省南充市川北医学院药物研究所,四川南充620000 [2]南充市中心医院骨关节疾病中心,四川南充637100 [3]西南医科大学附属自贡医院/自贡市精神卫生中心,四川自贡643020

出　　处：《沈阳药科大学学报》2024年第11期1476-1484,共9页Journal of Shenyang Pharmaceutical University

基　　金：四川省自然科学基金项目(2022NSFSC0609);四川省卫生健康委员会医学科技项目(21PJ196)。

摘　　要：目的通过肿瘤靶向多肽修饰脂质体载带抗血管药物贝伐单抗,增强抗血管药物的抑制肿瘤增殖和转移的效果。方法研究通过透射电镜和动态光散射对所设计的纳米药物进行形貌和粒径表征;通过细胞毒性实验验证纳米药物的体外安全性;通过Transwell实验验证所设计抗血管纳米药物的体外抑制迁移能力;通过肿瘤体积生长验证纳米药物的体内抗肿瘤效果;通过检测实验动物的血清生化指标检测纳米药物的体内安全性。结果纳米药物在体外呈现球状纳米颗粒的形貌,粒径为71 nm左右,对细胞无明显细胞毒性,体外也可以明显抑制肿瘤细胞的迁移,体内与生理盐水组相比可较明显的抑制肿瘤生长,又可明显减少肿瘤的肺转移。最重要的是,给药组小鼠的体重与对照组无明显变化与差异,说明所设计的纳米药物对小鼠的生长无明显影响,也无明显的肝肾毒性,具有较好的生物安全性。结论本研究所涉及的靶向型脂质体纳米药物为骨肉瘤的治疗提供了新的思路与方向。Objective A liposome modified with a targeted peptide was prepared to load the anti-vascular drug bevacizumab,and to investigate whether this strategy enhanced the inhibitory effect of bevacizumab on tumor proliferation and metastasis.Methods In this study,the morphology and particle size of the designed nanomedicine were characterized by transmission electron microscopy and dynamic light scattering.Cytotoxicity test was used to verify the safety of the nanomedicine in vitro.Transwell assay was used to verify the migration inhibition ability of the designed anti-angiogenesis nanomedicine in vitro.The anti-tumor effect of the nanomedicine in vivo was verified by measuring the tumor volume.The in vivo safety of the nanomedicine was tested by detecting serum biomarkers.Results The results showed that the nanomedicine had the morphology of spherical nanoparticles in vitro,and the particle size was about 71 nm.The nanomedicine had no obvious cytotoxicity to the cells tested.It significantly inhibited the migration of tumor cells in vitro and in vivo,and significantly reduced the lung metastasis of tumor.Most importantly,there was no significant change in the body weight of mice,indicating that the designed nanomedicine had no obvious effect on the growth of mice,nor obvious liver and kidney toxicity with good biological safety.Conclusion The targeted liposome nanomedicine in this study provides a new idea and direction for the treatment of osteosarcoma.

关 键 词：脂质体 抗血管新生 贝伐单抗 骨肉瘤 转移 

分 类 号：R96[医药卫生—药理学]