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化敌为友:具有双重免疫调节功能的先进“纳米疫苗”用于增强转移性三阴性乳腺癌的免疫治疗

Turning foes to friends: Advanced " nanovaccine" with dual immunoregulation for enhanced immunotherapy of metastatic triple-negative breast cancer.

作者信息

Wang Ze, Sha Tong, Li Jinwei, Luo Huanyu, Liu Annan, Liang Hao, Qiang Jinbiao, Li Lei, Whittaker Andrew K, Yang Bai, Sun Hongchen, Shi Ce, Lin Quan

机构信息

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, 130012, PR China.

Department of Oral Pathology, Hospital of Stomatology, Jilin University, Changchun, 130021, PR China.

出版信息

Bioact Mater. 2024 May 31;39:612-629. doi: 10.1016/j.bioactmat.2024.04.023. eCollection 2024 Sep.


DOI:10.1016/j.bioactmat.2024.04.023
PMID:38883315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11179173/
Abstract

As a "cold tumor", triple-negative breast cancer (TNBC) exhibits limited responsiveness to current immunotherapy. How to enhance the immunogenicity and reverse the immunosuppressive microenvironment of TNBC remain a formidable challenge. Herein, an " nanovaccine" Au/CuNDs-R848 was designed for imaging-guided photothermal therapy (PTT)/chemodynamic therapy (CDT) synergistic therapy to trigger dual immunoregulatory effects on TNBC. On the one hand, Au/CuNDs-R848 served as a promising photothermal agent and nanozyme, achieving PTT and photothermal-enhanced CDT against the primary tumor of TNBC. Meanwhile, the released antigens and damage-associated molecular patterns (DAMPs) promoted the maturation of dendritic cells (DCs) and facilitated the infiltration of T lymphocytes. Thus, Au/CuNDs-R848 played a role as an " nanovaccine" to enhance the immunogenicity of TNBC by inducing immunogenic cell death (ICD). On the other hand, the nanovaccine suppressed the myeloid-derived suppressor cells (MDSCs), thereby reversing the immunosuppressive microenvironment. Through the dual immunoregulation, "cold tumor" was transformed into a "hot tumor", not only implementing a "turning foes to friends" therapeutic strategy but also enhancing immunotherapy against metastatic TNBC. Furthermore, Au/CuNDs-R848 acted as an excellent nanoprobe, enabling high-resolution near-infrared fluorescence and computed tomography imaging for precise visualization of TNBC. This feature offers potential applications in clinical cancer detection and surgical guidance. Collectively, this work provides an effective strategy for enhancing immune response and offers novel insights into the potential clinical applications for tumor immunotherapy.

摘要

作为一种“冷肿瘤”,三阴性乳腺癌(TNBC)对当前的免疫疗法反应有限。如何增强TNBC的免疫原性并逆转其免疫抑制微环境仍然是一项艰巨的挑战。在此,设计了一种“纳米疫苗”Au/CuNDs-R848用于成像引导的光热疗法(PTT)/化学动力疗法(CDT)协同治疗,以触发对TNBC的双重免疫调节作用。一方面,Au/CuNDs-R848作为一种有前景的光热剂和纳米酶,实现了对TNBC原发肿瘤的PTT和光热增强CDT。同时,释放的抗原和损伤相关分子模式(DAMPs)促进了树突状细胞(DCs)的成熟并促进了T淋巴细胞的浸润。因此,Au/CuNDs-R848作为一种“纳米疫苗”,通过诱导免疫原性细胞死亡(ICD)来增强TNBC的免疫原性。另一方面,纳米疫苗抑制了髓源性抑制细胞(MDSCs),从而逆转了免疫抑制微环境。通过双重免疫调节,“冷肿瘤”转变为“热肿瘤”,不仅实施了“化敌为友”的治疗策略,还增强了对转移性TNBC的免疫治疗。此外,Au/CuNDs-R848作为一种出色的纳米探针,能够进行高分辨率近红外荧光和计算机断层扫描成像,以精确可视化TNBC。这一特性在临床癌症检测和手术指导中具有潜在应用。总的来说,这项工作为增强免疫反应提供了一种有效策略,并为肿瘤免疫治疗的潜在临床应用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/d8427e604239/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/fcaca58ff229/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/559aaadfc4e8/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/07316ff4e8c1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/08e644af46fd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4b40ac911f6a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4b80ac601ab7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/02f3c686639c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/18a7d12661fd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/84ba35a78678/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4d6784ebdce8/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/d8427e604239/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/fcaca58ff229/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/559aaadfc4e8/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/07316ff4e8c1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/08e644af46fd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4b40ac911f6a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4b80ac601ab7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/02f3c686639c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/18a7d12661fd/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/84ba35a78678/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/4d6784ebdce8/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a82/11179173/d8427e604239/gr9.jpg

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[2]
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[3]
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Front Transplant. 2025-4-24

[4]
Promising future of breast cancer vaccine asking for multidisciplinary collaboration: a literature review.

Front Cell Dev Biol. 2025-4-24

本文引用的文献

[1]
Immunoadjuvant-Modified Potentiate Cancer Photothermal Immunotherapy.

Nano Lett. 2024-1-10

[2]
One Stone, Three Birds: Multifunctional Nanodots as "Pilot Light" for Guiding Surgery, Enhanced Radiotherapy, and Brachytherapy of Tumors.

ACS Cent Sci. 2023-10-17

[3]
Spatial predictors of immunotherapy response in triple-negative breast cancer.

Nature. 2023-9

[4]
Pomegranate-inspired multifunctional nanocomposite wound dressing for intelligent self-monitoring and promoting diabetic wound healing.

Biosens Bioelectron. 2023-9-1

[5]
Multifunctional nano-system for multi-mode targeted imaging and enhanced photothermal therapy of metastatic prostate cancer.

Acta Biomater. 2023-8

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c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer.

J Am Chem Soc. 2023-4-26

[7]
Exposure of Immunogenic Tumor Antigens in Surrendered Immunity and the Significance of Autologous Tumor Cell-Based Vaccination in Precision Medicine.

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Rhythm Mild-Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma.

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Adv Sci (Weinh). 2022-11

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