Guan Peixin, Guo Zhanchen, Xu Shuxin, Lu Haifeng, Wang Lisheng, Gu Zikuan, Liu Zhen
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8 M5, Canada.
Angew Chem Int Ed Engl. 2023 Apr 17;62(17):e202301202. doi: 10.1002/anie.202301202. Epub 2023 Mar 10.
Harnessing innate immunity is an appealing strategy for cancer treatment. Herein, we report a new strategy called molecularly imprinted nanobeacons (MINBs) for redirecting innate immune killing towards triple-negative breast cancer (TNBC). The MINBs were molecularly imprinted nanoparticles with the N-epitope of glycoprotein nonmetastatic B (GPNMB) as the template and grafted with plentiful fluorescein moieties as the hapten. The MINBs could tag the TNBC cells via binding with GPNMB and thereby provide navigation for recruiting hapten-specific antibodies. The gathered antibodies could further trigger effective Fc-domain-mediated immune killing towards the tagged cancer cells. In vivo experiments showed that the TNBC growth was significantly inhibited after MINBs treatment by intravenous injection as compared with control groups. This study not only opens a new access for redirecting innate immunity towards TNBC but also paves the way for innate immunity-based therapy of other diseases.
利用先天免疫是一种有吸引力的癌症治疗策略。在此，我们报告一种名为分子印迹纳米信标（MINB）的新策略，用于将先天免疫杀伤重定向至三阴性乳腺癌（TNBC）。MINB是分子印迹纳米颗粒，以糖蛋白非转移性B（GPNMB）的N表位为模板，并接枝大量作为半抗原的荧光素部分。MINB可通过与GPNMB结合标记TNBC细胞，从而为招募半抗原特异性抗体提供导航。聚集的抗体可进一步触发针对标记癌细胞的有效Fc结构域介导的免疫杀伤。体内实验表明，与对照组相比，静脉注射MINB治疗后TNBC的生长受到显著抑制。本研究不仅为将先天免疫重定向至TNBC开辟了新途径，也为基于先天免疫的其他疾病治疗铺平了道路。
