AUTHOR=Chen Wen , Guo Fengjie , Ren Zhipeng , Wang Linghui , Li Tinghui , Hou Xiaobin TITLE=Aptamer-siRNA chimera and gold nanoparticle modified collagen membrane for the treatment of malignant pleural effusion JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.973892 DOI=10.3389/fbioe.2022.973892 ISSN=2296-4185 ABSTRACT=

Malignant pleural effusion is one of the most common complications of advanced lung cancer and there is no effective clinical treatment at present. Here, we constructed an aptamer-siRNA chimeras/PEI/PEG/gold nanoparticle (AuNP)/collagen membrane that can progressively activate T cells by layer by layer assembly. Electron microscope showed this collagen membrane could be divided into 10 layers with a total thickness of 50–80μm, and AuNPs could be observed. Aptamer-siRNA chimeras could bind specifically to OX40+ cells and silencing programmed death receptor-1 (PD-1) gene. In vitro experiments demonstrated that chimeras/PEI/PEG/AuNPs gradually activated T cells to continuously kill lung adenocarcinoma cells in malignant pleural effusion. Animal experiments showed that chimeras/PEI/PEG/AuNP/collagen membrane effectively treated malignant pleural effusion. Compared with PD-1 inhibitor group, the number of cancer cells, ki-67 proliferation index and CD44 expression in the pleural effusion was significantly decreased and the lymphocyte/cancer cell ratio was significantly increased in the chimeras/AuNP-CM group. Flow cytometry showed that compared with PD-1 inhibitor group, T cell number in the chimeras/AuNP-CM group was significantly increased, while the proportion of PD-1+ T cells was markedly decreased. In conclusion, we constructed an chimeras/PEI/PEG/AuNP/collagen membrane, which was more effective in the treatment of malignant pleural effusion, and had less side effects than PD-1 inhibitors.