Self-Adaptive Nanoregulator to Mitigate Dynamic Immune Evasion of Pancreatic Cancer
文献类型：期刊论文
| 作者 | Pan, Jiaxing4; Lai, Yi3; Zhang, Shunan3; Zhang, Huijuan3; Shan, Yiming3; Huang, Lujia3; Wang, Feng2; Yu, Haijun3 ; Xu, Leiming4; Xu, Zhiai1
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| 刊名 | ADVANCED MATERIALS
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| 出版日期 | 2023-10-18 |
| 页码 | 16 |
| 关键词 | cancer-associated fibroblasts immune evasion nanoregulator pancreatic ductal adenocarcinoma peptide-drug conjugate |
| ISSN号 | 0935-9648 |
| DOI | 10.1002/adma.202305798 |
| 通讯作者 | Lai, Yi(laiyi@simm.ac.cn) ; Yu, Haijun(hjyu@simm.ac.cn) ; Xu, Leiming(xuleiming@xinhuamed.com.cn) ; Xu, Zhiai(zaxu@chem.ecnu.edu.cn) |
| 英文摘要 | The advance of immunotherapy has shifted the paradigm of cancer management in clinics. Nevertheless, a considerable subset of pancreatic ductal adenocarcinoma (PDAC) patients marginally respond to current immunotherapy due to the occurrence of dynamic immune evasion arising from intrinsic and therapeutic stress. In this investigation, the pivotal role of pancreatic cancer-associated fibroblast (CAF)-induced fibrosis and tumor cell-mediated T-cell exhaustion in driving the dynamic immune evasion is identified. Building upon this discovery, the authors herein engineer a novel peptide-drug conjugate (PDC)-based self-adaptive nanoregulator for mitigating dynamic immune evasion of PDAC. The resulting nanoregulator can perform a two-stage morphology transformation from spherical micelle to nanofiber, and subsequently from nanofiber to spherical nanoparticles. Such kind of nanostructure design can facilitate differentialized delivery of CAF inhibitor in the extracellular matrix for intervening CAF-mediated tumor fibrosis, and indoleamine 2,3-dioxygenase 1 inhibitor to tumor cells for relieving IDO1-kynurenine axis-induced T-cell exhaustion. Antitumor study with the self-adaptive nanoregulator elicited persistent antitumor immunity and remarkable antitumor performance in both Panc02 and KPC tumor models in vivo. Taken together, the PDC-based self-adaptive nanoregulator may provide a novel avenue for enhanced PDAC immunotherapy. A peptide-drug conjugate (PDC)-based self-adaptive nanoregulator with first-stage spherical micelle to nanofiber, and second-stage nanofiber to spherical nanoparticles morphology transformation performance, is developed for tailoring dynamic immune evasion of PDAC. The nanoregulator is demonstrated to intervene in cancer-associated fibroblast-mediated tumor fibrosis and reverse 2,3-dioxygenase 1-kynurenine axis-involed T-cell exhaustion.image |
| WOS关键词 | FIBROBLASTS ; THERAPY |
| 资助项目 | J.P. and Y.L. contributed equally to this study. Financial support from the National Natural Science Foundation of China (82203041, U22A20328, 82102915, and 22074043), the Science and Technology Commission of Shanghai Municipality (23ZR1475000 and 20430711[82203041] ; J.P. and Y.L. contributed equally to this study. Financial support from the National Natural Science Foundation of China (82203041, U22A20328, 82102915, and 22074043), the Science and Technology Commission of Shanghai Municipality (23ZR1475000 and 20430711[U22A20328] ; J.P. and Y.L. contributed equally to this study. Financial support from the National Natural Science Foundation of China (82203041, U22A20328, 82102915, and 22074043), the Science and Technology Commission of Shanghai Municipality (23ZR1475000 and 20430711[82102915] ; J.P. and Y.L. contributed equally to this study. Financial support from the National Natural Science Foundation of China (82203041, U22A20328, 82102915, and 22074043), the Science and Technology Commission of Shanghai Municipality (23ZR1475000 and 20430711[22074043] ; National Natural Science Foundation of China[23ZR1475000] ; National Natural Science Foundation of China[20430711800] ; National Natural Science Foundation of China[LG-QS-202206-04] ; Science and Technology Commission of Shanghai Municipality[2021M00157] ; Science and Technology Commission of Shanghai Municipality[2021424] ; China Postdoctoral Science Foundation[BX20220320] ; China National Postdoctoral Program for Innovative Talents ; National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, CAS[2021-09-YHJ-06] ; National Facility for Protein Science in Shanghai (NFPS), Shanghai Advanced Research Institute, CAS[XHEC-D-2023-053] ; Shanghai Institute of Materia Medica, CAS ; Medical Ethics Committee of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics |
| 语种 | 英语 |
| WOS记录号 | WOS:001084195600001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/307403]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Lai, Yi; Yu, Haijun; Xu, Leiming; Xu, Zhiai |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China 2.Fudan Univ, Huadong Hosp, Shanghai Med Coll, Dept Gastroenterol, Shanghai 200040, Peoples R China 3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Shanghai Jiao Tong Univ, XinHua Hosp, Dept Gastroenterol, Sch Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pan, Jiaxing,Lai, Yi,Zhang, Shunan,et al. Self-Adaptive Nanoregulator to Mitigate Dynamic Immune Evasion of Pancreatic Cancer[J]. ADVANCED MATERIALS,2023:16. |
| APA | Pan, Jiaxing.,Lai, Yi.,Zhang, Shunan.,Zhang, Huijuan.,Shan, Yiming.,...&Xu, Zhiai.(2023).Self-Adaptive Nanoregulator to Mitigate Dynamic Immune Evasion of Pancreatic Cancer.ADVANCED MATERIALS,16. |
| MLA | Pan, Jiaxing,et al."Self-Adaptive Nanoregulator to Mitigate Dynamic Immune Evasion of Pancreatic Cancer".ADVANCED MATERIALS (2023):16. |
入库方式： OAI收割
来源：上海药物研究所
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