Advancing immunotherapy in triple negative breast Cancer: A novel multimodal theranostic nanoplatform integrating synergetic ferroptosis and photothermal therapy

作者全名：Cheng, Long; Qiu, Yibo; He, Lingyun; Wang, Haiyang; Zheng, Min; Wang, Ruoyao; Hu, Yaqin; Yu, Huilin; Luo, Wenpei; Xia, Yuanyou; Cao, Yang; Wang, Zhigang; Wang, Yingxiong; Ran, Haitao; Yang, Lu

作者地址：[Cheng, Long; He, Lingyun; Wang, Haiyang; Zheng, Min; Hu, Yaqin; Yu, Huilin; Luo, Wenpei; Cao, Yang; Wang, Zhigang; Ran, Haitao; Yang, Lu] Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China; [Cheng, Long; Qiu, Yibo; He, Lingyun; Wang, Haiyang; Zheng, Min; Wang, Ruoyao; Hu, Yaqin; Yu, Huilin; Luo, Wenpei; Xia, Yuanyou; Cao, Yang; Wang, Zhigang; Ran, Haitao; Yang, Lu] Chongqing Med Univ, Affiliated Hosp 2, Chongqing Key Lab Ultrasound Mol Imaging & Therapy, Chongqing 400010, Peoples R China; [Wang, Ruoyao; Yang, Lu] Chongqing Med Univ, Affiliated Hosp 2, Dept Breast & Thyroid Surg, Chongqing 400010, Peoples R China; [Qiu, Yibo; Wang, Yingxiong] Chongqing Med Univ, Sch Publ Hlth, Lab Reprod Biol, Chongqing 400016, Peoples R China

通信作者：Ran, HT; Yang, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Ultrasound, Chongqing 400010, Peoples R China.

来源：CHEMICAL ENGINEERING JOURNAL

ESI学科分类：ENGINEERING

WOS号：WOS:001208755500001

JCR分区：Q1

影响因子：13.3

年份：2024

卷号：485

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Triple negative breast cancer; Photothermal; Ferroptosis; Immunotherapy; Nano -medicine; Multi -modal imaging

摘要：Triple negative breast cancer (TNBC) is a subtype of breast cancer with high invasiveness and the worst prognosis. Immunotherapy has demonstrated significant potential in its treatment. However, the response rate remains unsatisfactory. In this work, we prepared multifunctional theranostic nanoplatforms (P-R@P/U-V) with synergetic ferroptosis and photothermal therapy (PTT) in improving TNBC tumor microenvironment for improving local treatment in situ, and synergistic anti-programmed cell death-ligand 1 (PD-L1) immunotherapy to prevent distant metastasis. With P-R@P/U-V, real-time monitoring of the specific distribution in tumors is possible due to the greatly improved ultrasound imaging (US), photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capabilities. Moreover, P-R@P/U-V has excellent photothermal conversion ability. Whereas PTT killed TNBC cells after laser irradiation, the liquid-gas phase transition not only improved US but also triggered controllable release of RSL3 in situ, enhancing ferroptosis of TNBC cells. Besides, the release of tumor-associated antigens (TAAs) increased via PTT and ferroptosis, strongly stimulating T cell activation, dendritic cell maturation, and anti-tumor cytokine secretion. The lung metastases of TNBC were significantly inhibited following the combined use of P-R@P/U-V and PD-L1 inhibitors. The multimodal and multifunctional nanoplatforms demonstrated excellent effects in early diagnosis and synergistic treatment of TNBC. This represents a novel strategy based on local treatment for additional enhanced anti-PD-L1 immunotherapy, with high clinical application prospects.

基金机构：University; Science and Technology Bureau of Yuzhong District, Chongqing [20200145]

基金资助正文：This work was financially supported by the National Natural Science Foundation of China (Grant Nos. 81701709) , the Senior Medical Talents Program of Chongqing for Young and Middle-aged, the Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medicalr University, and the Science and Technology Bureau of Yuzhong District, Chongqing (Grant Nos. 20200145) .