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首页> 外文期刊>Vaccine >Characterization of chemically defined poly-N-isopropylacrylamide based copolymeric adjuvants.
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Characterization of chemically defined poly-N-isopropylacrylamide based copolymeric adjuvants.

机译：化学定义的基于聚N-异丙基丙烯酰胺的共聚物助剂的表征。

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PNiPAAm is a thermo-responsive polymer with an adjuvant activity. To identify the minimal chemical structure present within PNiPAAm responsible for its adjuvant property, three different constituent polymers with specific functional groups were synthesized through free radical reaction and tested their adjuvant potential along with PNiPAAm. Among them, polymer with isopropyl attached to an amide showed maximal adjuvant activity in rodents followed by polymer with amide or ketone functional groups. However, secondary amine containing polymer did not show any adjuvant activity. In addition, to improve the adjuvant properties of PNiPAAm, we incorporated an affinity ligand, boronate. At first, we synthesized and characterized the dual responsive copolymers PNiPAAm-co-VPBA and PNiPAAm-co-VPBA-co-DMAEMA. Biocompatibility of these copolymers was confirmed both in vitro and in vivo. Mice injected with these copolymers mixed with collagen (CII) developed significant levels of anti-CII antibodies comprising of all the major IgG subclasses and an increased T cell activation. At the injection site, massive infiltration of immune cells was observed. However, only PNiPAAm-co-VPBA-co-DMAEMA-CII induced arthritis in mice after injection of 0.5 M fructose confirming the importance of effective release of CII from the polymer for its adjuvant activity. Thus, a fine balance of hydrophobicity and hydrophilicity promotes adjuvant properties and continuous release of antigen, in this case CII, from polymer is essential for its adjuvant activity.
机译：PNiPAAm是具有佐剂活性的热响应性聚合物。为了确定负责其佐剂性质的PNiPAAm中存在的最小化学结构，通过自由基反应合成了三种具有特定官能团的不同组成聚合物，并测试了它们与PNiPAAm的佐剂潜力。其中，异丙基与酰胺连接的聚合物在啮齿动物中表现出最大的佐剂活性，其次是具有酰胺或酮官能团的聚合物。但是，含仲胺的聚合物没有显示任何佐剂活性。此外，为了改善PNiPAAm的佐剂特性，我们引入了亲和配体硼酸酯。首先，我们合成并表征了双响应共聚物PNiPAAm-co-VPBA和PNiPAAm-co-VPBA-co-DMAEMA。在体外和体内都证实了这些共聚物的生物相容性。注射了这些与胶原蛋白（CII）混合的共聚物的小鼠产生了显着水平的抗CII抗体，其中包括所有主要的IgG亚类，并且T细胞活化增加。在注射部位，观察到免疫细胞大量浸润。然而，仅PNiPAAm-co-VPBA-co-DMAEMA-CII在注射0.5 M果糖后在小鼠中诱发了关节炎，证实了从聚合物中有效释放CII对其佐剂活性的重要性。因此，疏水性和亲水性的良好平衡促进了佐剂性质，并且从聚合物中连续释放抗原（在这种情况下为CII）对于其佐剂活性是必不可少的。

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