RGD肽修饰的pH响应型中空介孔二氧化硅纳米粒子的制备与评价  

Preparation and Evaluation of pH-Responsive Hollow Mesoporous Silica Nanoparticles Modified by RGD Peptides

作　　者：王小宁[1] 巩志强 闫梦茹 梁晓燕[1] 马远涛[1] WANG Xiaoning;GONG Zhiqiang;YAN Mengru;LIANG Xiaoyan;MA Yuantao(College of Pharmacy,Xi′an Medical University,Xi′an 710021,China)

机构地区：[1]西安医学院药学院,陕西西安710021

出　　处：《化学与生物工程》2021年第9期25-31,共7页Chemistry & Bioengineering

基　　金：陕西省教育厅专项科研计划项目(19JK0757);西安医学院青年科研基金项目(2018QN12);陕西省缺血性心血管疾病重点实验室开放基金项目(2017ZDKF09);中尼友好拉吉姆医学实验室开放基金项目(18LJM06);陕西省大学生创新创业训练项目(S202011840061)。

摘　　要：以聚多巴胺(PDA)为反应平台,对中空介孔二氧化硅纳米粒子(HMSN)进行RGD肽和聚(2-乙基-2-噁唑啉)(PEOz)双重修饰,构建了RGD肽和PEOz共同修饰的中空介孔二氧化硅纳米载体(HMSN-PEOz-RGD),以盐酸阿霉素(DOX)为模型药物构建载药体系DOX@HMSN-PEOz-RGD,用红外光谱法(FTIR)对载体进行结构表征,考察载药体系的载药量、包封率及载体的形态、粒径及Zeta电位,通过体外释药实验研究载药体系在不同pH值下的响应性释放,以人乳腺癌细胞MCF-7为模型,考察载体的生物相容性及载药体系的细胞毒性及细胞摄取过程。结果表明,HMSN-PEOz-RGD的平均粒径为(256.1±26.5)nm,粒径分布较均匀;DOX@HMSN-PEOz组和DOX@HMSN-PEOz-RGD组的体外释药都表现出明显的pH依赖性,即酸性(pH值5.0)条件下药物快速释放,而在生理pH值(pH值7.4)条件下药物释放缓慢;生物相容性实验结果显示,各载体在2.5~80μg·mL^(-1)的浓度范围内,与MCF-7细胞共培养24 h后,细胞存活率均在89%以上,表明载体具有良好的生物相容性;体外抗肿瘤活性实验结果表明,相比于其余载药制剂组,DOX@HMSN-PEOz-RGD组细胞的生长明显得到抑制,RGD修饰显著促进了DOX的细胞摄取。本研究所构建的纳米载体能够特异性靶向递送DOX,具有一定的应用前景。In this study,using polydopamine(PDA)as a reaction platform,we modified hollow mesoporous silica nanoparticles(HMSN)by RGD peptides and pH-responsive material poly(2-ethyl-2-oxazoline)(PEOz),constructed a hollow mesoporous silica nanocarrier HMSN-PEOz-RGD co-modified by RGD peptides and PEOz,and developed a drug delivery system DOX@HMSN-PEOz-RGD with Doxorubicin hydrochloride(DOX)as a model drug.Moreover,we characterized the structure of the carriers by FTIR,investigated the drug loading capacity,encapsulation efficiency of the drug delivery system,morphology,particle size,and Zeta potential of the carriers,and studied the responsive release of the drug delivery system at different pH values by in vitro drug release experiments.Furthermore,using human breast cancer cell MCF-7 as a model,we investigated the biocompatibility of the carriers,the cytotoxicity of the drug delivery system,and the process of cellular uptake.The results show that the average particle size of HMSN-PEOz-RGD is(256.1±26.5)nm,and the particle size distribution is uniform.Both the DOX@HMSN-PEOz and DOX@HMSN-PEOz-RGD groups show obvious pH-responsive release in vitro,that is,rapid release of drug under acidic(pH value 5.0)condition,but slow release under physiological pH(pH value 7.4)condition.The biocompatibility experiments results show that the survival rate of MCF-7 cells is more than 89%after co-culture of each carrier with MCF-7 cells for 24 h within the concentration range of 2.5-80μg·mL^(-1),indicating that the carriers have good biocompatibility.The results of in vitro antitumor activity experiments show that the growth of MCF-7 cells is significantly inhibited after co-cultured with DOX@HMSN-PEOz-RGD compared with other preparation groups,and the cellular uptake of DOX is significantly increased after RGD peptides modification.The nanocarrier constructed in this study can achieve the targeted delivery of DOX and has a certain application potential.

关 键 词：中空介孔二氧化硅纳米粒子 盐酸阿霉素 RGD肽 聚(2-乙基-2-噁唑啉) 

分 类 号：R943[医药卫生—药剂学] R979.1[医药卫生—药学]