Graphdiyne oxide nanosheets exert anti-lymphoma effect by killing cancer stem cells and remodeling tumor microenvironment

作者全名："Li, Jinxin; Wang, Qiwei; Lu, Huan; Han, Yingli; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Hou, Yu; Xu, Shuangnian; Xiong, Zecheng; Liu, Huibiao; Li, Yuliang; Chen, Chunying; Liu, Ying; Qian, Pengxu"

作者地址："[Li, Jinxin; Wang, Qiwei; Lu, Huan; Han, Yingli; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Qian, Pengxu] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Peoples R China; [Li, Jinxin; Wang, Qiwei; Lu, Huan; Han, Yingli; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Qian, Pengxu] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Bone Marrow Transplantat Ctr, Hangzhou 310058, Peoples R China; [Li, Jinxin; Wang, Qiwei; Lu, Huan; Han, Yingli; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Qian, Pengxu] Zhejiang Univ, Liangzhu Lab, Med Ctr, 1369 West Wenyi Rd, Hangzhou, Peoples R China; [Chen, Chunying; Liu, Ying] Natl Ctr Nanosci & Technol China, CAS Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China; [Chen, Chunying; Liu, Ying] Natl Ctr Nanosci & Technol China, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China; [Li, Jinxin; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Qian, Pengxu] Zhejiang Univ, Inst Hematol, Hangzhou 310058, Peoples R China; [Li, Jinxin; Jiang, Lingli; Qian, Wenchang; Zhu, Meng; Wang, Beini; Min, Jingshu; Qian, Pengxu] Zhejiang Engn Lab Stem Cell & Immunotherapy, Hangzhou 310058, Peoples R China; [Xiong, Zecheng; Liu, Huibiao; Li, Yuliang] Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, Key Lab Organ Solids, Beijing 100190, Peoples R China; [Chen, Chunying; Liu, Ying] Univ Chinese Acad Sci, Beijing 100049, Peoples R China; [Chen, Chunying; Liu, Ying] GBA Natl Inst Nanotechnol Innovat, Guangzhou 510700, Peoples R China; [Hou, Yu] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Xu, Shuangnian] Third Mil Med Univ, Southwest Hosp, Ctr Hematol, 30 Gaotanyan St, Chongqing 400038, Peoples R China"

通信作者："Liu, Y (通讯作者)，Natl Ctr Nanosci & Technol China, Beijing, Peoples R China.; Qian, PX (通讯作者)，Zhejiang Univ, Sch Med, Hangzhou, Peoples R China."

来源：NANO TODAY

ESI学科分类：PHYSICS

WOS号：WOS:000874221400003

JCR分区：Q1

影响因子：17.4

年份：2022

卷号：46

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Graphdiyne oxide; Lymphoma; Single -cell RNA-seq; Tumor microenvironment; Cancer -associated fibroblasts

摘要："Inflammatory and immunosuppressive tumor microenvironment (TME) is responsible for accelerating lymphoma initiation and progression. Graphdiyne oxide (GDYO) nanosheets have been shown to restrain tumor inflammation, remodel tumor microenvironment and suppress tumor growth. However, whether GDYO exerts anti-lymphoma effect has been elusive. Here, we first delineated the inflammatory and im-munosuppressive signature of lymphoma TME by bioinformatic analysis. We then demonstrated the toxic effects of GDYO on multiple types of lymphoma cells in vitro. Further xenograft experiments showed that GDYO significantly eliminated tumor initiation and growth in vivo. Moreover, single-cell transcriptome sequencing of tumor tissue revealed GDYO treatment remarkably decreased the frequencies of cancer stem cells, immunosuppressive Treg cells and pro-inflammatory myeloid cells. Mechanistically, GDYO treatment markedly inhibited the Mif-Ackr3 signaling in tumor cells and CAFs, reduced expression of inflammatory cytokines in CAFs, mitigated the number of Treg cells and CSCs, which ultimately suppressed the growth of lymphoma. Finally, we showed that GDYO showed excellent biosafety and biocompatibility. Together, our study demonstrates that GDYO exerts the duplex anti-lymphoma effects by simultaneously killing the cancer stem cells and remodeling the lymphoma TME, which provide a reference for the potential appli-cation of GDYO nanomaterials as a novel nanomedicine to treat lymphoma in the future.(c) 2022 Elsevier Ltd. All rights reserved."

基金机构："National Key R&D Program of China, Stem Cell and Translation Research [2018YFA0109300]; National Natural Science Foundation of China (NSFC) [82222003, 81870080, 91949115, 82161138028, 82000149, 31971318, 21790050, 21790053, 22071251, 21875258]; National Key R&D Program of China [2021YFA1200900]; Zhejiang Province Science Foundation for Distinguished Young Scholars [LR19H080001, LQ21H180006]; Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang [2020R01006]; China Postdoctoral Science Foundation (CPSF) [2021M702853]"

基金资助正文："This work was supported by grants from the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), the National Natural Science Foundation of China (NSFC) (82222003, 81870080, 91949115, 82161138028, 82000149, 31971318, 21790050, 21790053, 22071251 and 21875258), the National Key R&D Program of China (2021YFA1200900), Zhejiang Province Science Foundation for Distinguished Young Scholars (LR19H080001) and Exploration Project (LQ21H180006), the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (2020R01006), the China Postdoctoral Science Foundation (CPSF) (2021M702853). Thanks for the technical support by the Core Facilities, Zhejiang University School of Medicine."