Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

Yang, Kaiting; Han, Wenbo; Jiang, Xiaomin; Piffko, Andras; Bugno, Jason; Han, Chuanhui; Li, Sirui; Liang, Hua; Xu, Ziwan; Zheng, Wenxin; Wang, Liangliang; Wang, Jiaai; Huang, Xiaona; Fu, Yang–Xin; Lin, Wenbin; Weichselbaum, Ralph R.

doi:10.1038/s41565-022-01225-x

Cited by 78 publications

(48 citation statements)

References 47 publications

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“…The importance of specific cytokines and cell populations in the response to STING agonists remains unclear and is likely context dependent. For example, Yang et al (63) found that therapeutic response to an NP STING agonist was independent of both IFNAR1 and TNFα, whereas Kim and colleagues (32) found that IFN-I was important to efficacy and vascular normalization in response to intratumoral CDN administration. Therefore, it is likely that the nature, kinetics, and mechanism of vascular remodeling are dependent on several factors, including model and cancer type, dose, administration route, and immune status.…”

Section: Discussionmentioning

confidence: 99%

“…In conclusion, our results demonstrate that systemic administration of STANs provides a multimodal strategy for coordinating antitumor innate immunity and vascular normalization to enhance T cell infiltration and response to T cell-based immunotherapies. As STANs and other immunostimulatory nanomedicines (45,63,(65)(66)(67) advance toward translation, potential immunotoxicities must be further considered, and it will be important to optimize dosing regimens and to identify the proper clinical scenarios in which to deploy STANs. For example, a small study revealed that one injection of STANs could induce vascular normalization (fig.…”

Section: Discussionmentioning

confidence: 99%

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STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy

et al. 2023

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The tumor-associated vasculature imposes major structural and biochemical barriers to the infiltration of effector T cells and effective tumor control. Correlations between stimulator of interferon genes (STING) pathway activation and spontaneous T cell infiltration in human cancers led us to evaluate the effect of STING-activating nanoparticles (STANs), which are a polymersome-based platform for the delivery of a cyclic dinucleotide STING agonist, on the tumor vasculature and attendant effects on T cell infiltration and antitumor function. In multiple mouse tumor models, intravenous administration of STANs promoted vascular normalization, evidenced by improved vascular integrity, reduced tumor hypoxia, and increased endothelial cell expression of T cell adhesion molecules. STAN-mediated vascular reprogramming enhanced the infiltration, proliferation, and function of antitumor T cells and potentiated the response to immune checkpoint inhibitors and adoptive T cell therapy. We present STANs as a multimodal platform that activates and normalizes the tumor microenvironment to enhance T cell infiltration and function and augments responses to immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy

et al. 2023

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“…Recently, properly designed nanotechnologies have been exploited to improve adjuvant penetration and distribution to tumor tissues, with lipid nanodiscs and nanoscale coordination polymers developed as delivery vehicles. 24,55 Dane et al incorporated stimulator of interferon genes (STING)-activating cyclic dinucleotides (CDNs) into lipid nanodiscs (LNDs) by conjugating the PEGylated lipid with CDNs using a cleavable dialanine peptide linker (Fig. 6B).…”

Section: Tumor Tissue Penetration In Molecular Prr Agonist-based Adju...mentioning

confidence: 99%

Materials engineering strategies for cancer vaccine adjuvant development

Zhang

Yang

et al. 2023

Chem. Soc. Rev.

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“…In contrast to conventional nanoparticles, Lin et al. identified a tumor-targeting nanoscale coordination polymer (ZnCDA) loaded with CDA and zinc (Zn) ( 43 ). According to in vivo studies, intravenously administered ZnCDA prolongs CDA half-life and facilitates tumor targeting, providing an important pharmacokinetic advantage.…”

Section: Nanomedicine Targeting Activation Of Sting In the Cancer Imm...mentioning

confidence: 99%

Nanomedicines targeting activation of STING to reshape tumor immune microenvironment and enhance immunotherapeutic efficacy

et al. 2023

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Immunotherapy has greatly enhanced the effectiveness of cancer treatments, but the efficacy of many current immunotherapies is still limited by the tumor-suppressive immune microenvironment. Multiple studies have shown that activating the stimulation of IFN genes (STING) pathway and inducing innate immunity can significantly impact the tumor immune microenvironment and improve antitumor therapy. While natural or synthetic STING agonists have been identified or developed for preclinical and clinical use, small molecule agonists have limited utility due to degradation and lack of targeting. As such, the delivery and release of STING agonists into tumor tissue is a major challenge that must be addressed in order to further advance the use of STING agonists. To address this challenge, various nanomedicines have been developed. In this paper, we concisely review the antitumor immunotherapeutic mechanisms of STING agonists, highlighting the latest developments in STING agonists and the current progress of nanomedicines for activating STING. We classify the different nanomedicines according to the STING agonists they utilize in order to facilitate understanding of recent advances in this field. Finally, we also discuss the prospects and challenges of this field.

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Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration

Cited by 78 publications

References 47 publications

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy

STING-activating nanoparticles normalize the vascular-immune interface to potentiate cancer immunotherapy

Materials engineering strategies for cancer vaccine adjuvant development

Nanomedicines targeting activation of STING to reshape tumor immune microenvironment and enhance immunotherapeutic efficacy

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