Advanced search
1 file | 4.72 MB Add to list

Potent and prolonged innate immune activation by enzyme-responsive imidazoquinoline TLR7/8 agonist prodrug vesicles

Author
Organization
Abstract
Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators of antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from the site of injection into systemic circulation. Here, we report on the design and synthesis of an amphiphilic polymer-prodrug conjugate of an imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures of 200 nm. The conjugate contains an endosomal enzyme-responsive linker enabling degradation of the vesicles and release of the TLR7/8 agonist in native form after endocytosis, which results in high in vitro TLR agonist activity. In a mouse model, locally administered vesicles provoke significantly more potent and long-lasting immune stimulation in terms of interferon expression at the injection site and in draining lymphoid tissue compared to a nonamphiphilic control and the native TLR agonist. Moreover, the vesicles induce robust activation of dendritic cells in the draining lymph node in vivo.
Keywords
CANCER, NANOPARTICLES, RELEASE, NANOCAPSULES, RECEPTORS

Downloads

  • (...).pdf
    • full text (Published version)
    • |
    • UGent only
    • |
    • PDF
    • |
    • 4.72 MB

Citation

Please use this url to cite or link to this publication:

MLA
Wang, Bi, et al. “Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles.” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 142, no. 28, 2020, pp. 12133–39, doi:10.1021/jacs.0c01928.
APA
Wang, B., Van Herck, S., Chen, Y., Bai, X., Zhong, Z., Deswarte, K., … Shi, Y. (2020). Potent and prolonged innate immune activation by enzyme-responsive imidazoquinoline TLR7/8 agonist prodrug vesicles. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 142(28), 12133–12139. https://doi.org/10.1021/jacs.0c01928
Chicago author-date
Wang, Bi, Simon Van Herck, Yong Chen, Xiangyang Bai, Zifu Zhong, Kim Deswarte, Bart Lambrecht, et al. 2020. “Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles.” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142 (28): 12133–39. https://doi.org/10.1021/jacs.0c01928.
Chicago author-date (all authors)
Wang, Bi, Simon Van Herck, Yong Chen, Xiangyang Bai, Zifu Zhong, Kim Deswarte, Bart Lambrecht, Niek Sanders, Stefan Lienenklaus, Hans W. Scheeren, Sunil A. David, Fabian Kiessling, Twan Lammers, Bruno De Geest, and Yang Shi. 2020. “Potent and Prolonged Innate Immune Activation by Enzyme-Responsive Imidazoquinoline TLR7/8 Agonist Prodrug Vesicles.” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 142 (28): 12133–12139. doi:10.1021/jacs.0c01928.
Vancouver
1.
Wang B, Van Herck S, Chen Y, Bai X, Zhong Z, Deswarte K, et al. Potent and prolonged innate immune activation by enzyme-responsive imidazoquinoline TLR7/8 agonist prodrug vesicles. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. 2020;142(28):12133–9.
IEEE
[1]
B. Wang et al., “Potent and prolonged innate immune activation by enzyme-responsive imidazoquinoline TLR7/8 agonist prodrug vesicles,” JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 142, no. 28, pp. 12133–12139, 2020.
@article{8679093,
  abstract     = {{Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators of antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from the site of injection into systemic circulation. Here, we report on the design and synthesis of an amphiphilic polymer-prodrug conjugate of an imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures of 200 nm. The conjugate contains an endosomal enzyme-responsive linker enabling degradation of the vesicles and release of the TLR7/8 agonist in native form after endocytosis, which results in high in vitro TLR agonist activity. In a mouse model, locally administered vesicles provoke significantly more potent and long-lasting immune stimulation in terms of interferon expression at the injection site and in draining lymphoid tissue compared to a nonamphiphilic control and the native TLR agonist. Moreover, the vesicles induce robust activation of dendritic cells in the draining lymph node in vivo.}},
  author       = {{Wang, Bi and Van Herck, Simon and Chen, Yong and Bai, Xiangyang and Zhong, Zifu and Deswarte, Kim and Lambrecht, Bart and Sanders, Niek and Lienenklaus, Stefan and Scheeren, Hans W. and David, Sunil A. and Kiessling, Fabian and Lammers, Twan and De Geest, Bruno and Shi, Yang}},
  issn         = {{0002-7863}},
  journal      = {{JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}},
  keywords     = {{CANCER,NANOPARTICLES,RELEASE,NANOCAPSULES,RECEPTORS}},
  language     = {{eng}},
  number       = {{28}},
  pages        = {{12133--12139}},
  title        = {{Potent and prolonged innate immune activation by enzyme-responsive imidazoquinoline TLR7/8 agonist prodrug vesicles}},
  url          = {{http://doi.org/10.1021/jacs.0c01928}},
  volume       = {{142}},
  year         = {{2020}},
}

Altmetric
View in Altmetric
Web of Science
Times cited: