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

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.

SUBMITTER: Qin H

PROVIDER: S-EPMC10449932 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Qin Hao H Chen Yang Y Wang Zeming Z Li Nan N Sun Qing Q Lin Yixuan Y Qiu Wenyi W Qin Yuting Y Chen Long L Chen Hanqing H Li Yiye Y Shi Jian J Nie Guangjun G Zhao Ruifang R

Nature communications 20230824 1

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-initi ...[more]

PMID: 37620331

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Project description:The abnormal tumor vasculature presents a major challenge to the adequate delivery of chemotherapeutics, often limiting efficacy. We developed a nanoparticle-based technique to deliver localized mild hyperthermia (MHT) used to transiently alter tumor vascular transport properties and enhance transport of macromolecules into tumor interstitium. The strategy involved administering and localizing accumulation of stealth gold nanorods (GNRs, 103 μg of GNRs/g of tumor), and irradiating tumor with a low-photon laser flux (1 W/cm(2)) to generate MHT. The treatment increased vascular permeability within 24 h after treatment, allowing enhanced transport of macromolecules up to 54 nm in size. A mathematical model is used to describe changes in tumor mass transport properties where the rate of macromolecular exchange between interstitial and vascular region (R) and maximum dye enhancement (Ymax) of 23-nm dextran dye is analytically solved. During enhanced permeability, R increased by 200% while Ymax increased by 30% relative to untreated group in pancreatic CAPAN-1 tumors. MHT treatment also enhanced transport of larger dextran dye (54 nm) as assessed by intravital microscopy, without causing occlusive cellular damage. Enhanced vascular transport was prolonged for up to 24 h after treatment, but reversible with transport parameters returning to basal levels after 36 h. This study indicates that localized mild hyperthermia treatment opens a transient time-window with which to enable and augment macromolecule transport and potentially improve therapeutic efficacy. From the clinical editor: In this study, local intra-tumor mild hyperthermia is induced using a nanoparticle-based approach utilizing stealth gold nanorods and irradiating the tumor with low-photon laser flux, resulting in locally increased vascular permeability enabling enhanced delivery of therapeutics, including macromolecules up to 54 nm in size. Similar approaches would be very helpful in addressing treatment-resistant malignancies in clinical practice.

Dataset Information

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

Publications

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

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