具有pH响应性载硼替佐米纳米粒靶向治疗多发性骨髓瘤OA
pH-responsive bortezomib-loaded nanoparticles for targeted therapy of multiple myeloma
目的 制备一种靶向整合素αvβ3的载硼替佐米(bortezomib,BTZ)纳米粒(BTZ@PLGA-RGD),以实现多发性骨髓瘤(multiple myeloma,MM)的靶向治疗.方法 采用乳化蒸发法及碳二亚胺法制备BTZ@PLGA-RGD聚合物纳米粒,通过扫描电子显微镜(SEM)、粒度分析动态光散射法(DLS)和傅里叶变换红外光谱(FTIR)对BTZ@PLGA-RGD纳米粒进行表征,并分析其稳定性、包封率、体外释药和血液相容性.通过CCK-8法和激光共聚焦显微镜(CLSM)验证BTZ@PLGA-RGD纳米粒对细胞的毒性作用和细胞内的定位情况.结果 BTZ@PLGA-RGD纳米粒大小均匀,呈球形,平均粒径为(113.7±3.1)nm,表面带正电荷,电位为(+6.4±1.3)mV,包封率为73.32%,稳定性和血液相容性均良好,具有pH响应性,在pH 5.5缓冲液中,48 h BTZ累计释放量达(82.34±0.12)%.FTIR分析表明BTZ@PLGA-RGD纳米粒成功负载BTZ,且RGD肽成功偶联在其表面.根据细胞定位实验发现,因RGD肽介导的主动靶向作用使BTZ@PLGA-RGD纳米粒被RPMI8226细胞摄入更多,且其可实现溶酶体逃逸.CCK-8实验结果表明,BTZ@PLGA-RGD对RPMI8226细胞具有更强的毒性作用.结论 BTZ@PLGA-RGD具有良好的稳定性、水溶性、靶向性、可控释药性及生物安全性,为MM靶向治疗提供新的研究策略.
Objective The BTZ@PLGA-RGD nanoparticles that target integrin αvβ3 and are loaded with bortezomib(BTZ)were prepared to achieve targeted therapy for multiple myeloma(MM).Methods The emul-sion solvent evaporation method and carbodiimide chemistry method were used to form BTZ@PLGA-RGD nanopar-ticles.The characterization of BTZ@PLGA-RGD nanoparticles was confirmed with scanning electron microscopy(SEM),dynamic light scattering(DLS),and fourier-transform infrared(FTIR).BTZ@PLGA-RGD nanoparticles were evaluated in terms of stability,encapsulation efficiency,release profile,and blood compatibility.The local-ization and cytotoxicity of BTZ@PLGA-RGD were determined using confocal laser scanning microscopy(CLSM)and the CCK-8 experiment.Results BTZ@PLGA-RGD nanoparticles were in a spherical shape with a uniform size distribution.The mean particle size of BTZ@PLGA-RGD nanoparticles was(113.7±3.1)nm,accompanied by a positive surface charge of(+6.4±1.3)mV.The entrapment efficiency of the BTZ@PLGA-RGD nanoparticles was 73.32%.These nanoparticles exhibited good long-term stability and blood compatibility.BTZ@PLGA-RGD nanoparticles had pH-responsive drug release properties,and the cumulative drug release(%)over 48 h was(82.34±0.12)%.FTIR analysis indicated that BTZ was successfully loaded into the BTZ@PLGA-RGD nanopar-ticles,and RGD was successfully immobilized on the surface of the nanoparticles.The localization analysis showed that the active targeting effect mediated by the RGD peptide enabled the BTZ@PLGA-RGD nanoparticles to be taken up by RPMI8226 cells more efficiently,and these nanoparticles could achieve lysosome escape.The CCK-8 experimental results indicated that BTZ@PLGA-RGD nanoparticles exhibited stronger cytotoxicity against RPMI8226 cells.Conclusion BTZ@PLGA-RGD demonstrates outstanding stability,water solubility,targeting ability,controlled drug-release properties,and biological safety,offering a novel research strategy for MM targeted therapy.
尹茉莉;罗文彬;罗思宇;林夕塞;陈三强;孙美艳
吉林医药学院检验学院(吉林吉林 132013)吉林医药学院检验学院(吉林吉林 132013)西安交通大学第二附属医院(陕西西安 710000)吉林医药学院检验学院(吉林吉林 132013)吉林医药学院检验学院(吉林吉林 132013)吉林医药学院检验学院(吉林吉林 132013)
医药卫生
硼替佐米多发性骨髓瘤纳米粒表征靶向治疗
bortezomibmultiple myelomananoparticlescharacterizationtargeting therapy
《实用医学杂志》 2026 (6)
959-968,10
国家自然科学基金资助项目(编号:32573352)吉林省科技厅项目(编号:20230101263JC)吉林省大学生创新创业训练项目(编号:S202413706028)
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