Transiently thermoresponsive acetal polymers for safe and effective administration of Amphotericin B as a vaccine adjuvant
- Author
- Simon Van Herck (UGent) , Lien Van Hoecke (UGent) , Benoit Louage (UGent) , Lien Lybaert (UGent) , Ruben De Coen (UGent) , Sabah Kasmi (UGent) , Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens (UGent) , Xavier Saelens (UGent) and Bruno De Geest (UGent)
- Organization
- Abstract
- The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant. We present a new class of transiently thermoresponsive polymers that, in their native state, have a phase-transition temperature below room temperature but gradually transform into fully soluble polymers through acetal hydrolysis at endosomal pH values. RAFT polymerization afforded well-defined block copolymers that self-assemble into micellar nanoparticles and efficiently encapsulate AmpB. Importantly, nanoencapsulation strongly reduced the cytotoxic effect of AmpB but maintained its TLR-triggering capacity. Studies in mice showed that AmpB-loaded nanoparticles can adjuvant an RSV vaccine candidate with almost equal potency as a highly immunogenic oil-in-water benchmark adjuvant.
- Keywords
- RESPIRATORY SYNCYTIAL VIRUS, LINKED TLR AGONISTS, IMMUNE-RESPONSES, DRUG-DELIVERY, CANCER-IMMUNOTHERAPY, CYTOKINE RELEASE, NANOPARTICLES, TOXICITY, NANOGELS, PROTEIN
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8583911
- MLA
- Van Herck, Simon, et al. “Transiently Thermoresponsive Acetal Polymers for Safe and Effective Administration of Amphotericin B as a Vaccine Adjuvant.” BIOCONJUGATE CHEMISTRY, vol. 29, no. 3, 2018, pp. 748–60, doi:10.1021/acs.bioconjchem.7b00641.
- APA
- Van Herck, S., Van Hoecke, L., Louage, B., Lybaert, L., De Coen, R., Kasmi, S., … De Geest, B. (2018). Transiently thermoresponsive acetal polymers for safe and effective administration of Amphotericin B as a vaccine adjuvant. BIOCONJUGATE CHEMISTRY, 29(3), 748–760. https://doi.org/10.1021/acs.bioconjchem.7b00641
- Chicago author-date
- Van Herck, Simon, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, et al. 2018. “Transiently Thermoresponsive Acetal Polymers for Safe and Effective Administration of Amphotericin B as a Vaccine Adjuvant.” BIOCONJUGATE CHEMISTRY 29 (3): 748–60. https://doi.org/10.1021/acs.bioconjchem.7b00641.
- Chicago author-date (all authors)
- Van Herck, Simon, Lien Van Hoecke, Benoit Louage, Lien Lybaert, Ruben De Coen, Sabah Kasmi, Aaron P Esser-Kahn, Sunil A David, Lutz Nuhn, Bert Schepens, Xavier Saelens, and Bruno De Geest. 2018. “Transiently Thermoresponsive Acetal Polymers for Safe and Effective Administration of Amphotericin B as a Vaccine Adjuvant.” BIOCONJUGATE CHEMISTRY 29 (3): 748–760. doi:10.1021/acs.bioconjchem.7b00641.
- Vancouver
- 1.Van Herck S, Van Hoecke L, Louage B, Lybaert L, De Coen R, Kasmi S, et al. Transiently thermoresponsive acetal polymers for safe and effective administration of Amphotericin B as a vaccine adjuvant. BIOCONJUGATE CHEMISTRY. 2018;29(3):748–60.
- IEEE
- [1]S. Van Herck et al., “Transiently thermoresponsive acetal polymers for safe and effective administration of Amphotericin B as a vaccine adjuvant,” BIOCONJUGATE CHEMISTRY, vol. 29, no. 3, pp. 748–760, 2018.
@article{8583911,
abstract = {{The quest for new potent and safe adjuvants with which to skew and boost the immune response of vaccines against intracellular pathogens and cancer has led to the discovery of a series of small molecules that can activate Toll-like receptors (TLRs). Whereas many small molecule TLR agonists cope with a problematic safety profile, amphotericin B (AmpB), a Food and Drug Administration approved antifungal drug, has recently been discovered to possess TLR-triggering activity. However, its poor aqueous solubility and cytotoxicity at elevated concentrations currently hampers its development as a vaccine adjuvant. We present a new class of transiently thermoresponsive polymers that, in their native state, have a phase-transition temperature below room temperature but gradually transform into fully soluble polymers through acetal hydrolysis at endosomal pH values. RAFT polymerization afforded well-defined block copolymers that self-assemble into micellar nanoparticles and efficiently encapsulate AmpB. Importantly, nanoencapsulation strongly reduced the cytotoxic effect of AmpB but maintained its TLR-triggering capacity. Studies in mice showed that AmpB-loaded nanoparticles can adjuvant an RSV vaccine candidate with almost equal potency as a highly immunogenic oil-in-water benchmark adjuvant.}},
author = {{Van Herck, Simon and Van Hoecke, Lien and Louage, Benoit and Lybaert, Lien and De Coen, Ruben and Kasmi, Sabah and Esser-Kahn, Aaron P and David, Sunil A and Nuhn, Lutz and Schepens, Bert and Saelens, Xavier and De Geest, Bruno}},
issn = {{1043-1802}},
journal = {{BIOCONJUGATE CHEMISTRY}},
keywords = {{RESPIRATORY SYNCYTIAL VIRUS,LINKED TLR AGONISTS,IMMUNE-RESPONSES,DRUG-DELIVERY,CANCER-IMMUNOTHERAPY,CYTOKINE RELEASE,NANOPARTICLES,TOXICITY,NANOGELS,PROTEIN}},
language = {{eng}},
number = {{3}},
pages = {{748--760}},
title = {{Transiently thermoresponsive acetal polymers for safe and effective administration of Amphotericin B as a vaccine adjuvant}},
url = {{http://doi.org/10.1021/acs.bioconjchem.7b00641}},
volume = {{29}},
year = {{2018}},
}
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