如何逆转肿瘤微环境的免疫抑制效应已成为提高目前肿瘤疫苗临床疗效过程中亟待解决的关键科学问题。多肽类STAT3抑制剂因其特异性强、毒副作用低而在阻断相应信号转导通路，继而修复免疫抑制性肿瘤微环境中具有不可替代的作用。然而稳定性差、血浆清除率高、细胞膜渗透性低的体内行为使多肽在临床应用中受到很大限制。为此，本项目拟在纳米受限环境下构筑尺寸可控性的糖基纳米球晶化自组装物，相较于传统纳米载体具有非化学交联、肽负载量大、血浆稳定性高以及环境敏感性等优势。负载STAT3靶标肽的多功能纳米球晶可介导其胞内转运，通过靶向阻断免疫调节相关信号转导通路逆转肿瘤微环境中的免疫抑制效应，从而改善DCs肿瘤疫苗的免疫治疗效果。该递送系统的构建模式及相关研究国内外未见报道，对其胞内转运及与肿瘤疫苗协同治疗的作用机制进行研究，对于提高活性肽的成药性以及有效逆转肿瘤疫苗治疗过程中的免疫抑制效应，具有重大的理论和实践意义。

How to reverse the immune suppressive effect of tumor microenvironment has become a key scientific problem to be solved in the course of clinical efficacy of tumor vaccine. Because of the high specificity and low toxicity, the peptide inhibitors have an irreplaceable role in blocking the STAT3 signal transduction pathway, and then repair the immune suppressive tumor microenvironment. However, the low stability, high plasma clearance and poor cell membrane permeability in vivo restrict their clinical application. Therefore in this project, we proposed to construct the spherical crystallized polysaccharide self-assembly with controllable size under the nano confined environment. Compared to conventional nano-gel carriers, the vehicles possess advantages of non-chemical crosslinking, high loading capacity for peptide, plasma stability and environmental sensitivity. The multifunctional nano-spherulites can mediate the loaded STAT3 target peptides to intracellular transport, and then to reverse the immune suppression effect in tumor microenvironment by targeted blocking the signal transduction pathway. Therefore the improved Immune therapeutic effects of DCs tumor vaccine are expected. The construction mode of the delivery system and the related research have not been reported in the world. Studying the action mechanism of their intracellular transport and synergistic treatment with tumor vaccine, has great theoretical and practical significance to improve the druggability of target peptide and effectively reverse the immune suppressive effect during tumor vaccine therapy.