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生物合成的金纳米颗粒可激活 Toll 样受体并引发局部光转换的高热以实现多效性肿瘤免疫调节。

Biosynthesized gold nanoparticles that activate Toll-like receptors and elicit localized light-converting hyperthermia for pleiotropic tumor immunoregulation.

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, P. R. China.

Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.

出版信息

Nat Commun. 2023 Aug 24;14(1):5178. doi: 10.1038/s41467-023-40851-4.

Abstract

Manipulating the tumor immune contexture towards a more active state can result in better therapeutic outcomes. Here we describe an easily accessible bacterial biomineralization-generated immunomodulator, which we name Ausome (Au + [exo]some). Ausome comprises a gold nanoparticle core covered by bacterial components; the former affords an inducible hyperthermia effect, while the latter mobilizes diverse immune responses. Multiple pattern recognition receptors actively participate in Ausome-initiated immune responses, which lead to the release of a broad spectrum of pro-inflammatory cytokines and the activation of effector immune cells. Upon laser irradiation, tumor-accumulated Ausome elicits a hyperthermic response, which improves tissue blood perfusion and contributes to enhanced infiltration of immunostimulatory modules, including cytokines and effector lymphocytes. This immune-modulating strategy mediated by Ausome ultimately brings about a comprehensive immune reaction and selectively amplifies the effects of local antitumor immunity, enhancing the efficacy of well-established chemo- or immuno-therapies in preclinical cancer models in female mice.

摘要

操纵肿瘤免疫微环境使其向更活跃的状态转变,可以带来更好的治疗效果。在这里,我们描述了一种易于获取的细菌生物矿化产生的免疫调节剂,我们将其命名为 Ausome(Au + [exo]some)。Ausome 由一个金纳米颗粒核心组成,表面覆盖有细菌成分;前者提供诱导性的热疗效应,而后者则调动多种免疫反应。多种模式识别受体积极参与 Ausome 引发的免疫反应,导致释放广泛的促炎细胞因子,并激活效应免疫细胞。激光照射后,肿瘤中积累的 Ausome 会引发热疗反应,改善组织血液灌注,并有助于增强免疫刺激模块的浸润,包括细胞因子和效应淋巴细胞。Ausome 介导的这种免疫调节策略最终会引发全面的免疫反应,并选择性放大局部抗肿瘤免疫的效果,增强女性小鼠临床前癌症模型中已确立的化疗或免疫疗法的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/40ad/10449932/1ae01073e0fa/41467_2023_40851_Fig1_HTML.jpg

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