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Immunochemotherapy mediated by thermosponge nanoparticles for synergistic anti-tumor effects
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-11-22 , DOI: 10.1016/j.jconrel.2017.11.037
Yongdan Zhao , Qingle Song , Yijia Yin , Tingting Wu , Xiaomeng Hu , Xueqin Gao , Gao Li , Songwei Tan , Zhiping Zhang

The efficacy of immunotherapy was demonstrated to be compromised by reduced immunogenicity of tumor cells and enhanced suppressive properties of the tumor microenvironment in cancer treatment. There is growing evidence that low-dose chemotherapy can modulate the immune system to improve the anti-tumor effects of immunotherapy through multiple mechanisms, including the enhancement of tumor immunogenicity and reversal of the immunosuppressive tumor microenvironment. Here, we fabricated thermosponge nanoparticles (TSNs) for the co-delivery of chemotherapeutic drug paclitaxel (PTX) and immunostimulant interleukin-2 (IL-2) to explore the synergistic anti-tumor effects of chemotherapy and immunotherapy. The distinct temperature-responsive swelling/deswelling character facilitated the effective post-entrapment of cytokine IL-2 in nanoparticles by a facile non-solvent mild incubation method with unaffected bioactivity and favorable pharmacokinetics. PTX and IL-2 co-loaded TSNs exhibited significant inhibition on tumor growth and metastasis, and prolonged overall survival for tumor-bearing mice compared with the corresponding monotherapies. The synergistic effect was evidenced from the remodeled tumor microenvironment in which low-dose chemotherapeutics disrupted the immunosuppressive tumor microenvironment and enhanced tumor immunogenicity, and immunostimulant cytokine promoted the anti-tumor immune response of immune effector cells. The immunochemotherapy mediated by this thermosponge nanoplatform may provide a promising treatment strategy against cancer.



中文翻译:

热海绵纳米粒子介导的免疫化学疗法具有协同抗肿瘤作用

事实证明,免疫疗法的功效因肿瘤细胞免疫原性降低和肿瘤微环境在癌症治疗中抑制特性的增强而受到损害。越来越多的证据表明,低剂量化学疗法可以通过多种机制来调节免疫系统,从而提高免疫疗法的抗肿瘤效果,包括增强肿瘤的免疫原性和逆转免疫抑制性肿瘤微环境。在这里,我们制造了热海绵纳米颗粒(TSNs),用于化学药物紫杉醇(PTX)和免疫刺激性白介素2(IL-2)的共同递送,以探索化学疗法和免疫疗法的协同抗肿瘤作用。独特的温度响应性溶胀/溶胀特性通过一种不受影响的生物活性和良好的药代动力学的简便的非溶剂温和孵育方法,促进了细胞因子IL-2在纳米颗粒中的有效包埋。与相应的单一疗法相比,PTX和IL-2共装载的TSN对肿瘤的生长和转移具有明显的抑制作用,并且荷瘤小鼠的总生存期延长。重塑的肿瘤微环境证明了协同作用,其中低剂量化学疗法破坏了免疫抑制性肿瘤微环境并增强了肿瘤的免疫原性,免疫刺激性细胞因子促进了免疫效应细胞的抗肿瘤免疫反应。

更新日期:2017-11-22
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