基于生物分子的PD-L1siRNA多功能纳米递送体系用于小细胞肺癌靶向成像及免疫治疗研究

小细胞肺癌恶性程度高，转移早而广泛，进展迅速，极易产生耐药性，被认为是最难攻克的恶性肿瘤之一，临床上至今尚无有效的早期诊断方法及靶向治疗药物。本项目拟将适体介导分子识别技术、生物纳米技术及分子影像学有机结合，构建基于生物分子的多功能纳米成像探针用于小细胞肺癌的高灵敏、靶向识别及免疫治疗。有别于传统的抗体类免疫检查点疗法，本项目将基于RNA干扰技术选择性、高效地沉默小细胞肺癌过度表达的PD-L1基因，有望从根本上大幅度降低癌细胞的免疫逃逸及免疫耐受。同时，利用纳米探针的成像功能对siRNA的递送及免疫治疗进行原位、实时、动态监测，在保证治疗效果的同时显著降低治疗副作用和治疗成本。因此，该项目的实施有利于推动我国抢占小细胞肺癌研究制高点，并对其它恶性肿瘤的靶向诊疗提供新思路。

Small cell lung cancer (SCLC), one of the most aggressive solid tumors, is characterized by high malignancy, early and extensive metastasis, rapid tumor growth, and very strong drug resistance. However, there is no effective methods for its early diagnosis and corresponding targeting drugs. In this project, the aptamer-based molecular recognition, nanotechnology, and molecular imaging are integrated to construct multifunctional biomolecule-based nanoprobes for targeted imaging and immunotherapy of SCLC. Differing from widely studied antibody-derived immune checkpoint inhibitors, RNA interference technology is applied in this project to effectively and selectively knockdown the expression of PD-L1 that is over expressed in SCLC, thus essentially inhibiting the immune escape and immune resistance of the cancer cells. Moreover, real-time tracking of siRNA biodistribution and therapeutic effect can be obtained for personalized theranostics with minimized systemic toxicity. This project will be greatly significant because it can not only promote our country to occupy a commanding height in the research field of SCLC, but also provide new tools for treatment of other advanced cancers.