论文部分内容阅读
为实现化学疗法与免疫疗法的联合应用,本研究合成了具有还原响应性的紫杉醇(Paclitaxel,PTX)前药PEG-SS-PTX,并以此为载体包载吲哚胺2,3-双加氧酶(Indoleamine 2,3-dioxygenase,IDO)抑制剂CY-1-4制备PEG-SS-PTX/CY-1-4 NPs.通过细胞毒作用、免疫原性细胞死亡(Immunogenic cell death,ICD)诱导能力和抗肿瘤功效对PEG-SS-PTX/CY-1-4 NPs进行评估.动态光散射(Dynamic light scattering,DLS)结果显示PEG-SS-PTX/CY-1-4 NPs粒径约为149 nm.体外实验结果表明PEG-SS-PTX/CY-1-4 NPs的细胞毒性具有浓度依赖性,并且能够引发B16-F10细胞的ICD.体内实验结果表明PEG-SS-PTX/CY-1-4 NPs在小鼠黑色素瘤模型中能够显著抑制肿瘤生长,降低IDO在肿瘤组织中的表达,并且能够增加脾脏中CD8+T细胞比例.综上,PEG-SS-PTX/CY-1-4 NPs达到良好抗肿瘤效果的同时降低了化疗药物的给药剂量,是一种安全有效的联合递送平台.“,”In order to realize the combination of chemotherapy and immunotherapy,a reduction-responsive paclitaxel(PTX)prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 NPs.PEG-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity,immunogenic cell death(ICD)induction ability and anti-tumor efficacy.Dynamic light scattering(DLS)results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 nm.In vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner,and it induced the ICD of B16-Fl0 cells.In vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor tissues.Moreover,it increased the rate of CD8+T cells in the spleen.In summary,PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs,which was a safe and effective combined delivery system.