光热Fe3O4纳米粒子诱导的免疫性铁突变用于协同治疗结直肠癌。

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Nanobiotechnology Pub Date : 2024-10-16 DOI:10.1186/s12951-024-02909-3
Yue Li, Jia Chen, Qi Xia, Jing Shang, Yujie He, Zhi Li, Yingying Chen, Feng Gao, Xi Yu, Zeting Yuan, Peihao Yin
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引用次数: 0

摘要

光热疗法(PTT)是一种前景广阔的非侵入性疗法,在消除肿瘤方面显示出巨大的潜力。它不仅能诱导癌细胞凋亡,还能引发免疫性细胞死亡(ICD),从而激活免疫系统对抗癌症。然而,免疫抑制性肿瘤微环境(TIME)对单次治疗引发强烈的免疫反应构成了挑战,从而限制了癌症免疫疗法的治疗效果。在这项研究中,双靶向纳米递送系统(GOx@FeNPs)与αPD-L1免疫检查点阻断剂相结合,可通过介导PTT、铁突变和抗肿瘤免疫反应抑制结直肠癌(CRC)的进展。简而言之,GOx@FeNPs中的环精氨酸甘氨酰天冬氨酸(cRGD)肽和茴香酰胺(AA)实现了特异性肿瘤递送,不仅具有良好的光热效应,可实现PTT和诱导ICD,还能消耗谷胱甘肽(GSH),催化内源性H2O2产生活性氧(ROS)。所有这些都加速了芬顿反应,增强了 PTT 诱导 ICD 的过程。因此,大量肿瘤特异性抗原被释放出来,刺激淋巴结中树突状细胞(DCs)的成熟,并增强 CD8+ T 细胞对肿瘤的浸润。同时,与αPD-L1联用对CRC具有良好的协同作用,抑瘤率超过90%。此外,由于Fe3+的存在,GOx@FeNPs在T2加权下具有良好的磁共振成像(MRI)能力,有利于CRC的综合诊断和治疗系统。通过构建双靶向GOx@FeNPs纳米平台,实现了PTT与铁突变的协同作用,提高了免疫治疗效果,为CRC免疫治疗提供了一种新方法。
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Photothermal Fe3O4 nanoparticles induced immunogenic ferroptosis for synergistic colorectal cancer therapy.

Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA)  in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H2O2. All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8+ T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe3+, which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy.

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来源期刊
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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