Potentiating dual-directional immunometabolic regulation with nanomedicine to enhance anti-tumor immunotherapy following incomplete photothermal ablation

作者全名：Jiang, Qinqin; Qiao, Bin; Zheng, Jun; Song, Weixiang; Zhang, Nan; Xu, Jie; Liu, Jia; Zhong, Yixin; Zhang, Qin; Liu, Weiwei; You, Lanlan; Wu, Nianhong; Liu, Yun; Li, Pan; Ran, Haitao; Wang, Zhigang; Guo, Dajing

作者地址：[Jiang, Qinqin; Qiao, Bin; Zheng, Jun; Liu, Weiwei; Wu, Nianhong; Li, Pan; Ran, Haitao; Wang, Zhigang] Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Song, Weixiang; Xu, Jie; Liu, Jia; Zhong, Yixin; Liu, Yun; Guo, Dajing] Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Zhang, Nan] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med Ultrason, Guangzhou 510080, Peoples R China; [Zhang, Qin] Chongqing Hosp Tradit Chinese Med, Dept Radiol, Chongqing 400021, Peoples R China; [You, Lanlan] Chengdu Med Coll, Clin Med Coll, Dept Ultrasound, Chengdu 610500, Peoples R China; [You, Lanlan] Chengdu Med Coll, Affiliated Hosp 1, Chengdu 610500, Peoples R China

通信作者：Wang, ZG (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Ultrasound Mol Imaging, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China.; Guo, DJ (通讯作者)，Chongqing Med Univ, Dept Radiol, Affiliated Hosp 2, Chongqing 400010, Peoples R China.

来源：JOURNAL OF NANOBIOTECHNOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001253216700001

JCR分区：Q1

影响因子：10.6

年份：2024

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Photothermal therapy; Adenosine metabolism; Immune checkpoint blockade; Immunosuppressive microenvironment; Biomaterials

摘要：Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

基金机构：National Natural Science Foundation of China [82172092, 82271970, 82202181, 82001823]; Postdoctoral Project of Chongqing Science Foundation [CSTB2023NSCQ-BHX0122, CSTB2023NSCQ-BHX0016]; Guangdong Basic and Applied Basic Research Foundation [2021A1515110102]; Guangzhou Special Research Topic of Basic and Applied Basic Research (Young Doctor "Sailing" Project) [2024A04J4638]; Program for Youth Innovation in Future Medicine of Chongqing Medical University [W0170]; Chongqing scientific research institutions performance incentive and guidance project [jxyn2021-2-13]

基金资助正文：This work was supported by the National Natural Science Foundation of China (grant nos. 82172092, 82271970, 82202181, 82001823), Postdoctoral Project of Chongqing Science Foundation (CSTB2023NSCQ-BHX0122, CSTB2023NSCQ-BHX0016), Guangdong Basic and Applied Basic Research Foundation (2021A1515110102), Guangzhou Special Research Topic of Basic and Applied Basic Research (Young Doctor "Sailing" Project) (2024A04J4638), Program for Youth Innovation in Future Medicine of Chongqing Medical University (grant No. W0170), Chongqing scientific research institutions performance incentive and guidance project(jxyn2021-2-13).