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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

24卷

期数:

2018年02期

页码:

122-130

栏目:

出版日期:

2018-03-20

文章信息/Info

Title:

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

作者:

朱颖₁; ₂; 张岩₁; 陈研₁; 杨晓英₁

1.天津医科大学药学院，天津市临床药物关键技术重点实验室，天津300070；2.天津医科大学第二医院药学部，天津300211

Author(s):

ZHU Ying₁; ₂;  ZHANG Yan₁;  CHEN Yan₁;  YANG Xiao-ying₁

1. School of Pharmacy, Tianjin Medical University, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin 300070，China; 2.Department of Pharmacy，The Second Hospital, Tianjin Medical University, Tianjin 300211, China

关键词:

沉淀聚合; 肿瘤靶向; CT造影剂; 药物输送

Keywords:

precipitation polymerization;  tumor targeting;  CT contrast agent;  drug delivery

分类号:

O63

DOI:

-

文献标志码:

A

摘要:

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-AuNP，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（AuNP）。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AuNP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pH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-AuNP纳米粒子在浓度低于100 μg/mL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。

Abstract:

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 with 2-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 of 135 nm 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 of 51.3% and their release showed pH dependence. In vitro drug delivery study indicated that the nanoparticles with FA modification could deliver DOX into MCF-7 cells more efficiently than the nanoparticles without functionalization of FA. The results of cytotoxicity assay indicated that the nanoparticles had no marked toxicity to MCF-7 cells at the concentration below 100 μg/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.

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备注/Memo

备注/Memo:

文章编号 １００６－８１４７（２０18）０2-0122-09
基金项目 天津市应用基础与前沿技术研究计划基金资助项目（15JCZDJC36300）；天津市自然科学基金资助项目（17JCQNJC14100）
作者简介 朱颖（1987-），女，药师，硕士在读，研究方向：药剂学；通信作者：杨晓英， E-mail：yangxiaoying@tmu.edu.cn。

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更新日期/Last Update: 2018-03-20