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

• Published in: Nature communications Vol. 14; no. 1; pp. 5178 - 20
• Main Authors: Qin, Hao, Chen, Yang, Wang, Zeming, Li, Nan, Sun, Qing, Lin, Yixuan, Qiu, Wenyi, Qin, Yuting, Chen, Long, Chen, Hanqing, Li, Yiye, Shi, Jian, Nie, Guangjun, Zhao, Ruifang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/21; 13/31; 13/51; 14; 14/19; 147/135; 147/143; 38/91; 631/250/251/1567; 639/925/352/2733; 692/4028/67/1059/2325; 82/80; Animal models; Anticancer properties; Antitumor activity; Bacteria; Cancer; Cell activation; Cytokines; E coli; Effector cells; Fever; Gold; Humanities and Social Sciences; Hyperthermia; Immune response; Immune system; Immunomodulation; Immunomodulators; Immunoregulation; Immunostimulation; Inflammation; Irradiation; Lymphocytes; Metastases; Mineralization; multidisciplinary; Nanoparticles; Pattern recognition; Pattern recognition receptors; Proteins; Science; Science (multidisciplinary); Toll-like receptors; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40851-4

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. Bacteria have been exploited as a potential bio-factory for the synthesis of nanoparticles. Here the authors report the generation of gold nanoparticles from Escherichia coli and show their application for eliciting hyperthermia and anti-tumor immune responses in preclinical cancer models.