核化学与放射化学2018，Vol.40Issue(1)：74-80,7.DOI:10.7538/hhx.2017.YX.2016091
靶向整合素αvβ3受体的新型RGDyC-PEG-PAMAM纳米探针的设计制备、131I标记及其质量控制
Design and Preparation of Novel RGDyC-PEG-PAMAM Nanoprobe Targeting Integrin αvβ3 Receptor, 131I Labeling and Its Quality Control
摘要
Abstract
In this study,arginine-glycine-aspartic acid(RGD) with tumor targeting was attached to the polyamidoamine dendrimers(PAMAM) with excellent biological properties as the nanocarrier labeled with radionuclide 131I.The pharmacodynamic properties of the labeled compounds in vivo and in vitro were evaluated,and the possibility of applying them to tumor-specific imaging and targeted therapy was discussed.The structure of the peptide Arg-Gly-Asp-Tyrosine-Cysteine(RGDyC) was determined by the chemical modification method,and then the double functional group(NHS-PEG-MAL,PEG) was introduced by the chemical method of click chemistry using "one pot two step" preparation.Nanocomposites were characterized by 1H NMR and UV spectroscopy.And then particle size distribution and potential were detected.The morphology and size distribution were characterized by transmission electron microscopy(TEM).Chloramine T method was used to label 131I,and the labeling rate,marker stability and water partition coefficient were determined.The yield of RGDyC-PEG-PAMAM nanocomposite is 62.09％.The labeling rate of RGDyC-PEGPAMAM is 94.68％-98.87％.The radiochemical purity of the marker in vitro is above 80％.Water partition coefficient,lg P(n-octanol/water) is-1.59±0.09.The designed RGDyC-PEG-PAMAM can successfully complete the 131I labeling with the chloramine T method.The preparation and labeling process is efficient and simple.The labeling product 131I-RGDyC-PEG-PAMAM has good stability,high hydrophilicity and good druggability.The results laid the foundation of pharmacodynamics study in vivo and in vitro,including further assess of the tumor cell uptake and growth inhibition in vitro,human tumor xenograft model therapy and tumor imaging.The results show that 131I-RGDyC-PEG-PAMAM can be used as a novel SPECT probe for tumor-specific imaging and targeted therapy.关键词
聚酰胺-胺树状大分子/131I标记/放射性同位素/整合素αvβ3Key words
polyamidoamine dendrimers/131I labeling/radioisotopes/integrins αvβ3分类
医药卫生引用本文复制引用
钟建秋,张金赫,王欣璐,陈永明,尹吉林,杨玉婷,吴凡,李华安,梁大成,褚曰环..靶向整合素αvβ3受体的新型RGDyC-PEG-PAMAM纳米探针的设计制备、131I标记及其质量控制[J].核化学与放射化学,2018,40(1):74-80,7.基金项目
广东省自然科学基金资助项目(2016A030313612) （2016A030313612）
