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环境响应纳米颗粒原位转化巨噬细胞表型用于肿瘤免疫治疗
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摘要
免疫治疗是目前非常有效的一种肿瘤治疗手段,许多研究结果表明调控免疫系统对抗肿瘤治疗具有重要作用。但是免疫细胞在肿瘤发展过程中也会发挥促进作用,比如影响肿瘤的发生,生长及转移。因此,调控免疫系统使其发挥正向的治疗效果也是目前研究的重要问题之一。基于此我们设计并合成了一种对肿瘤微环境的酸性响应的聚氨酯类高分子材料,通过温和的麦克尔加成获得这种聚合物,然后通过复乳法包载白介素-12(IL-12)形成IL-12P纳米颗粒。纳米尺寸的IL-12P纳米颗粒能够通过EPR效应被动靶向到肿瘤区域,并在微环境的酸性作用下释放出IL-12,调控浸润在实体瘤内部的巨噬细胞,使其由促肿瘤的M2表型向具有抗肿瘤的M1型转变,从而发挥抑制肿瘤生长的作用。这种方法能很好地规避免疫细胞不能有效浸润实体瘤的问题,对肿瘤免疫治疗的思路有新启发。
Immunotherapy has become a promising treatment for a variety of cancers and researchers realized that regulating immune system from accomplice to soldier was a very important issue. Re-educating immune cells was very important but less investigated. We developed tumor microenvironment responsive materials which are capable of effective functional conversion toward enhanced antitumor effects. The IL-12 encapsulated nanoparticles(IL-12P) could accumulate in tumor site and release IL-12 to reverse the infiltrated TAMs, which achieved therapeutic effect regardless of the immune cells infiltration barrier. The research implied us that locally regulate immune cells phenotype would contribute to the subsequent antitumor response for immunotherapy.
引文
[1]Bronte,V.;Murray,P.J.Nat Med 2015,21,117.
    [2]Watkins,S.K.;Egilmez,N.K.;Suttles,J.;Stout,R.D.J.Immunol.2007,178,1357

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