树枝状高分子修饰的水溶性近红外二区荧光聚合物的合成及其在肿瘤相关抗原载运中的应用  

NIR-ⅡFluorescence Probe Based on Polyamidoamine Dendrimers for Immunotherapy as Antigen Carrier

作　　者：王超[1] 孙鹏飞[1] 范曲立[1] ChaoWang;Peng-fei Sun;Qu-li Fan(State Key Laboratory for Organic Electronics and Information Displays&Institute of Advanced Materials(IAM),Nanjing University of Posts&Telecommunications,Nanjing 210023)

机构地区：[1]南京邮电大学有机电子与信息显示国家重点实验室信息材料与纳米技术研究院,南京210023

出　　处：《高分子学报》2022年第2期174-184,共11页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21674048,21604042);江苏省自然科学基金(基金号BK20201380)资助项目.

摘　　要：通过在具有供体-受体-供体结构的近红外二区(NIR-Ⅱ)荧光分子(TTQ-F)的侧链上修饰聚酰胺-胺型树枝状高分子(PAMAM)合成了一种NIR-Ⅱ荧光高分子(TTQ-F-PAMAM).该树枝状修饰的高分子不仅可以实现在900~1200 nm近红外二区范围的荧光成像,同时有着良好的光稳定性.PAMAM作为一种三维、高度有序的新型高分子,可以控制和设计分子的大小与功能基团,且具有较好的水溶性与单分散性.而TTQ-F-PAMAM上独特的PAMAM结构所带来的大量氨基,使其对卵清蛋白(OVA)的包载率可以达到16.43%.更重要的是,负载OVA的同时,可以有效载运至树突状细胞(dendritic cell,DC)内,并在其细胞环境中加速OVA的释放从而进一步激活DC的免疫反应.具体表现为DC细胞膜表面共刺激因子CD80和CD86的表达大大提高,以及分泌肿瘤坏死因子-α(tumor necrosisfactor-α,TNF-α)和白细胞介素-12p70(Interleukin-12p70,IL-12p70)的能力增强.本工作不仅实现了对肿瘤相关抗原的载运以及对抗原提呈细胞的激活,而且其近红外成像能力可以为今后的免疫治疗研究提供新的策略与方法.In this study,we design and synthesize a second near-infrared window(NIR-Ⅱ)fluorescence molecule(TTQ-F-PAMAM)by modifying polyamidoamine dendrimers on donor-acceptor-donor(D-A-D)NIRⅡfluorescence core TTQ-F.TTQ-F-PAMAM can realize fluorescence image during 900-1200 nm excited by 808 nm laser,and shows outstanding photostability.According to the dynamic light scattering(DLS)and transmission electron microscopy(TEM)results,the hydrodynamic size of TTQ-F-PAMAM was approximately 45 nm.As shown in the NIR-Ⅱimages of TTQ-F-PAMAM at different depths,the tissue penetration of NIR-Ⅱfluorescence signal from TTQ-F-PAMAM can reach up to 4 mm.Owing to the polyamidoamine dendrimers,TTQ-F-PAMAM showed great antigen-loading capacity.And the MTT assay showed that TTQ-F-PAMAM exerted lower cell toxicity on cells.Ovalbumin(OVA),a model antigen in immune research,could be adsorbed onto TTQ-F-PAMAM by electrostatic binding.The loading capacity of TTQ-F-PAMAM was 16.43%.TTQ-F-PAMAM@OVA,the nanoparticles loaded with antigen can easier transported to antigen presenting cells than free OVA.Dendritic cell(DC)is the major antigen presenting cell in innate immunity and plays an important role in cancer suppression.After cell uptake of TTQ-F-PAMAM@OVA,the antigen induces the maturation of DC and promotes specific anti tumor immunity.Compared with other groups,the percentage of both CD80 and CD86 significantly increased after cultured with [e-mail] cells activated by TTQ-F-PAMAM can release tumor necrosis factor-α(TNF-α)and interleukin-12p70(IL-12p70).The secretion of TNF-αand IL-12p70 from DCs incubated with TTQ-F-PAMAM@OVA was much higher than that incubated with free TTQ-F-PAMAM or OVA.TTQ-F PAMAM was used not only as a NIR-Ⅱfluorescence probe,but also as the delivery of proteins to antigen presenting cells.This treatment strategy may greatly improve the efficiency of cancer therapy and provides a new method for immunotherapy research.

关 键 词：树枝状高分子 近红外二区荧光成像 抗原蛋白负载 

分 类 号：TQ317[化学工程—高聚物工业] TQ460.4