Beyond Blocking: Engineering RNAi-Mediated Targeted Immune Checkpoint Nanoblocker Enables T-Cell-lndependent Cancer Treatment
文献类型：期刊论文
| 作者 | Han, Xiaoyan1; Wang, Linlin1; Li, Ting1; Zhang, Jiahui2; Zhang, Dailiang1; Li, Jili1; Xia, Yinghao1; Liu, Yanlan1; Tan, Weihong1,3,4 |
| 刊名 | ACS NANO
 |
| 出版日期 | 2020-12-22 |
| 卷号 | 14 |
| ISSN号 | 1936-0851 |
| 关键词 | immune checkpoint blockade RNAi engineering nanostructure NSCLC cancer immunotherapy |
| DOI | 10.1021/acsnano.0c08022 |
| 通讯作者 | Liu, Yanlan(ylliu@hnu.edu.cn) ; Tan, Weihong(tan@hnu.edu.cn) |
| 英文摘要 | The emergence of immune checkpoint blockade to activate host T cells to attack tumor cells has revolutionized the cancer treatment landscape over the past decade. However, sustained response has only been achieved in a small proportion of patients. This can be attributed to physiological barriers, such as T-cell heterogeneity and immunosuppressive tumor microenvironments. To this can be added obstacles intrinsic to traditional antibody-driven blockade methods, including the inability to inhibit checkpoint translocation from cytoplasm, systemic immune toxicity, and "bite back" effect on T cells. Using non-small cell lung cancer (NSCLC) as the cancer model, here we report an unconventional, yet powerful, tumor-targeted checkpoint blocking strategy by RNAi nanoengineering for T-cell-independent cancer therapy. Unlike antibodies, such nanoblocker silences both membranous and cytoplasmic PD-L1 in cancer cells, thus eliminating the binding step. Moreover, it is demonstrated that silencing of PD-L1 by the nanoblocker can cause the direct programmed cell death of NSCLC H460 cells, without the need of T-cell intervention. In vivo results from xenograft tumor models further demonstrate that tumor-homing peptide modification enables the nanoblocker to accumulate in the tumor tissue, downregulate the PD-L1 expression, and inhibit the tumor growth more efficiently than the nontargeted group. These findings may offer an effective means toward overcoming barriers against traditional checkpoint blockade and provide different insights into the molecular mechanism(s) underlying immunotherapy. |
| WOS关键词 | NANOPARTICLES ; BLOCKADE ; GENE ; ACTIVATION ; STRATEGIES ; MECHANISM ; APOPTOSIS ; REQUIRES ; ANTIBODY ; THERAPY |
| 资助项目 | National Natural Science Foundation of China (NSFC)[21827811] ; National Natural Science Foundation of China (NSFC)[21877031] ; Science and Technology Innovation Program of Hunan Province[2018RS3043] ; Science and Technology Innovation Program of Hunan Province[2017XK2103] ; Key R&D Program of Hunan Province[2019SK2201] ; Young Thousand Talents Program of China |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:000603308800110 |
| 资助机构 | National Natural Science Foundation of China (NSFC) ; Science and Technology Innovation Program of Hunan Province ; Key R&D Program of Hunan Province ; Young Thousand Talents Program of China |
| 源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/120026]  |
| 专题 | 中国科学院合肥物质科学研究院 |
| 通讯作者 | Liu, Yanlan; Tan, Weihong |
| 作者单位 | 1.Hunan Univ, Coll Chem & Chem Engn, Aptamer Engn Ctr Hunan Prov, Mol Sci & Biomed Lab,State Key Lab Chemo Biosensi, Changsha 410082, Hunan, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China 3.Shanghai Jiao Tong Univ, Coll Chem & Chem Engn, Sch Med, Renji Hosp,Inst Mol Med, Shanghai 200040, Peoples R China 4.Chinese Acad Sci, Canc Hosp, Univ Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Zhejiang, Peoples R China |
| 推荐引用方式 GB/T 7714 | Han, Xiaoyan,Wang, Linlin,Li, Ting,et al. Beyond Blocking: Engineering RNAi-Mediated Targeted Immune Checkpoint Nanoblocker Enables T-Cell-lndependent Cancer Treatment[J]. ACS NANO,2020,14. |
| APA | Han, Xiaoyan.,Wang, Linlin.,Li, Ting.,Zhang, Jiahui.,Zhang, Dailiang.,...&Tan, Weihong.(2020).Beyond Blocking: Engineering RNAi-Mediated Targeted Immune Checkpoint Nanoblocker Enables T-Cell-lndependent Cancer Treatment.ACS NANO,14. |
| MLA | Han, Xiaoyan,et al."Beyond Blocking: Engineering RNAi-Mediated Targeted Immune Checkpoint Nanoblocker Enables T-Cell-lndependent Cancer Treatment".ACS NANO 14(2020). |
入库方式： OAI收割
来源：合肥物质科学研究院
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。