Quercetin-ferrum nanoparticles enhance photothermal therapy by modulating the tumor immunosuppressive microenvironment

肿瘤微环境 纳米壳 癌症研究 免疫疗法 光热治疗 免疫系统 癌症免疫疗法 四平无引线包 医学 免疫学 材料科学 纳米技术 纳米颗粒 胶粘剂 图层(电子)
作者
Lin Li,Mengxing Zhang,Tiantian Liu,Jing Li,Shili Sun,Junjie Chen,Zhenmi Liu,Zhirong Zhang,Ling Zhang
出处
期刊:Acta Biomaterialia [Elsevier]
卷期号:154: 454-466 被引量:34
标识
DOI:10.1016/j.actbio.2022.10.008
摘要

Photothermal therapy (PTT) was reported to induce synergistic immunogenic cell death (ICD) which may convert tumor cells into "therapeutic vaccines". However, this is often insufficient to prevent tumor recurrence, in part because of the immunosuppressive microenvironment in tumors. Therefore, remodeling tumor microenvironment is of great importance to enhance the therapeutic efficacy of PTT. We herein fabricated a versatile nano-photosensitizer by assembling quercetin and Ferrum ion (QFN). The released quercetin from QFN could reduce programmed death ligand 1 (PD-L1) in tumor cells by inhibiting the phosphorylation of JAK2 and STAT3, and reshape extracellular matrix (ECM) by down-regulating α-SMA+ fibroblast in tumors. Moreover, QFN could capture tumor antigen and deliver it to the tumor-draining lymph nodes after PTT, which further enhanced the activation of antigen-presenting cells. As a result, QFN-based PTT eliminated melanoma and induced long-term immune memory to prevent tumor metastasis and recurrence. This study provides an effective and translationally feasible photothermic agent for photothermal/immunotherapy. STATEMENT OF SIGNIFICANCE: The efficacy of photothermal therapy (PTT) in cancer treatment is often limited by the immunosuppressive microenvironment in tumors. Herein, we prepared a versatile photosensitizer by assembling quercetin and Ferrum ion (QFN). Upon near-infrared light irradiation, QFN-PTT induced cancer cells destruction and tumor antigen release. QFN then captured antigen and delivered it to the tumor-draining lymph nodes, thus promoting dendritic cell maturation and T cells activation. Quercetin released from QFN in tumors improved T cells infiltration and activation in tumor by regulating immunosuppressive microenvironment. The QFN-PTT-treated mice exhibited significantly elongated survival time, and gained strong anti-tumor immune memory to prevent tumor metastasis and recurrence. Thus, this work provided a simple and versatile photothermic agent, and it has important implications for designing effective and translationally feasible photosensitizers for PTT.
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