恶性肿瘤的早期诊疗依赖精准医疗技术进步，而制备靶向性纳米药物用于抗肿瘤研究是精准医疗领域聚焦的关键问题，但一般纳米药物受制于复杂的生理环境而无法满足高精准度的要求。针对该问题，本项目拟通过DNA适体功能单体靶向肿瘤细胞表面高表达的受体、进而在活细胞周围原位合成分子印迹人工抗体作为靶向性纳米药物。前期研究表明，血管生成素的高分子抑制剂可以抑制其核糖核酸活性并降低其胞内外水平，进而抑制肿瘤细胞增殖。基于此，本项目拟在人工抗体中引入该抑制功能，以期实现肿瘤靶向和肿瘤抑制的双重作用。研究过程中，我们将通过上转换纳米颗粒引发自由基介导的硫醇-烯点击化学反应来实现原位合成技术突破，设计DNA结构域来实现pH响应性释放血管生成素小分子抑制剂，并深入探讨该人工抗体抑制肿瘤和阻断血管生成的机理。预计本项目的顺利开展将有助于肿瘤靶向抗体设计和肿瘤早期精准诊疗技术发展。

The early diagnosis and treatment of malignant tumors depends on the advancement of technologies related to precision medicine. Currently, the preparation of targeted nanodrugs for antitumor research is a key issue in the field of precision medicine. However, ordinary nanodrugs cannot meet the requirements of high accuracy due to the complex physiological environment. To address this problem, this project intends to target highly expressed receptors on the surface of tumor cells through DNA aptamer-based functional monomers, then perform in-situ synthesis of molecularly imprinted artificial antibodies around the live cells. Previous studies have shown that polymer inhibitors of angiogenin could inhibit tumor cell proliferation by suppressing the ribonucleic activity of angiogenin and decreasing angiogenin level inside and outside tumor cells. Based on this, the project intends to introduce this inhibitory function into artificial antibodies, with a view to achieving the dual role of tumor targeting and tumor suppression. In the research process, we will achieve a breakthrough in in-situ synthesis by using upconverting nanoparticles to initiate the free radical-mediated thiol-ene click chemistry, design DNA motifs for the pH-responsive drug release of angiogenin inhibitors, and explore in-depth the mechanism of antitumor effect and angiogenesis blocking therapy caused by artificial antibodies. It is expected that the smooth development of this project will contribute to the design of tumor-targeting antibodies and the advancement of technologies related to precision medicine.