靶向髓源性抑制细胞的抗肿瘤免疫红细胞膜包裹纳米药物设计和机制研究

Myeloid derived suppressor cells (MDSCs) play fundamental roles in immunosuppression and immune escape to promote tumor progression, which have emerged as an important therapeutic target to improve immunotherapy. However, the poor characteristics of drug candidates targeting MDSCs have impeded its translation to clinics, including low stability, poor specificity, and low security. The technology of erythrocyte membrane-camouflaged polymeric nanoparticles can be used as a new drug carrier to improve the pharmacokinetic and pharmacodynamic properties, which will contribute to overcome the bottlenecks of drugs targeting MDSCs. Thus, the aim of this project is to reverse the activity of MDSCs using erythrocyte membrane-camouflaged polymeric nanoparticles, which will specifically target MDSCs in tumor tissue and enhance the anti-tumor immunity, ultimately inhibiting tumor progression and metastasis. Firstly, we will design and characterize the erythrocyte membrane-camouflaged polymeric nanoparticles. Then its functional roles in inhibiting MDSCs and tumor suppression will be detected, after validating its specificity on tumor MDSCs. Furthermore, we will explore the underlying mechanism of tumor suppression and evaluate the safety properties. This study will open a new avenue for erythrocyte membrane-camouflaged drug development targeting MDSCs, which not only improve the efficiency of immunotherapeutic, but provide promicing drugs for anti-tumor therapy.

髓源性抑制细胞在肿瘤组织中发挥了重要的免疫抑制和免疫逃逸作用，靶向髓源性抑制细胞的策略将有助于改善目前抗肿瘤免疫疗法的疗效。目前，靶向髓源性抑制细胞的药物存在稳定性差、靶向性差、安全性不好等问题，极大程度上限制了其药物研发的进程。红细胞膜包裹纳米颗粒作为新兴的药物输运载体，解决了传统药物的药代动力学和药效学问题，具有解决靶向髓源性抑制细胞药物研发瓶颈的潜力。本项目将利用新型的红细胞膜包裹纳米颗粒载体特异性靶向逆转肿瘤组织中MDSCs的免疫抑制活性，从而增强抗肿瘤免疫应答，抑制肿瘤的生长和转移。我们将构建和表征特异性靶向肿瘤MDSCs的红细胞膜包裹纳米颗粒，检测其对肿瘤MDSCs、肿瘤生长和转移的抑制作用，进一步检测其体内分布，并对其进行安全性评价，阐明其发挥免疫抑制功能的分子作用机理，为改善抗肿瘤免疫治疗奠定基础，为其成为一种潜在的抗肿瘤免疫治疗药物提供理论依据。

本项目构建并表征了特异性靶向肿瘤MDSCs的红细胞膜包裹纳米颗粒，检测了纳米颗粒对肿瘤MDSCs、肿瘤生长和转移的抑制作用。其体内分布的检测和安全性评价仍在进行中。我们的研究工作正在为改善抗肿瘤免疫治疗奠定基础。