用于肿瘤靶向性X线CT造影剂和抗肿瘤药物传递的多功能含碘纳米粒子的制备和表征

Preparation and characterization of the multi-functional iodine-containing nanoparticles used as tumor targeted X-ray CT contrast agent and anti-cancer drug delivery

目的:制备用于肿瘤靶向性X线CT造影剂和抗肿瘤药物传递的多功能含碘纳米粒子,用于肿瘤诊断和治疗。方法:利用沉淀聚合法制备含碘聚合物纳米粒子P(MATIB-co-MBA-co-GMA)-FA-Au NP,该纳米粒子以2-甲基丙烯酰(3-酰胺-2,4,6-三碘苯甲酸)(MATIB)为单体,以N,N′-亚甲基双丙烯酰胺为交联剂(MBA),通过甲基丙烯酸缩水甘油酯(GMA)和乙二胺(EDA)将叶酸分子修饰到该纳米粒子表面,并原位沉积金纳米粒子(Au NP)。结果:TEM结果显示该纳米粒子分散均匀,平均粒径为135 nm。体外X线CT成像检测结果表明Au NP的掺杂显著增加了该纳米粒子的X线衰减性能。该纳米粒子同时可高效负载抗肿瘤药物(DOX),载药量为51.3%,并具有p H敏感的可控释放性能。体外药物输送结果显示有FA修饰的纳米粒子能更好地携载抗肿瘤药物进入肿瘤细胞。细胞毒性的结果显示该P(MATIB-co-MBA-co-GMA)-FA-Au NP纳米粒子在浓度低于100μg/m L时未显示明显毒性。载药后,有叶酸修饰的纳米粒子对肿瘤细胞具有更好的杀伤性能。结论:该纳米粒子可同时作为肿瘤靶向性X线CT造影剂和抗肿瘤药物载体,用于肿瘤诊断和治疗。

Objective:To prepare the multi-functional iodine-containing nanoparticles used as tumor targeted X-ray CT contrast agent and anti-cancer drug delivery for applications in tumor diagnosis and therapy.Methods:The iodine-containing polymer nanoparticles P(MATIB-co-MBA-co-GMA)-FA-AuNP)were prepared by precipitation polymerization with2-methacryl(3-amide-2,4,6-triiodobenzoic acid)(MATIB)as the monomer and N,N-methylene bisacrylamide(MBA)as the crosslinker.Folic acid molecules were modified onto the nanoparticles via the conjugation of glycidyl methacrylate(GMA)and ethane diamine(EDA).Gold nanoparticles(AuNP)were then deposited on the nanoparticles in situ.Results:From the observation of TEM images,the nanoparticles with the average size of135nm dispersed well.The results of in vitro CT imaging showed that the X-ray attenuation performance of the nanoparticles doping with AuNP was better than that of the nanoparticles without AuNP.In addition,the anti-cancer drugs doxorubicin hydrochloride(DOX)could be efficiently loaded onto the nanoparticles with a high loading capacity of51.3%and their release showed pH dependence.In vitro drug delivery study indicated that the nanoparticles with FA modification could deliver DOX into MCF-7cells more efficiently than the nanoparticles without functionalization of FA.The results of cytotoxicity assay indicated that the nanoparticles had no marked toxicity to MCF-7cells at the concentration below100μg/mL.The nanoparticles with FA modification showed much higher efficiency to kill tumour cells than the nanoparticles without FA after them loading with DOX.Conclusion:It is suggested that the P(MATIB-co-MBA-co-GMA)-FA-AuNP nanoparticles could be used as X-ray CT contrast agent and anti-cancer drug carriers at the same time for tumor diagnosis and treatment.