Počet záznamů: 1
pH and ROS responsiveness of polymersome nanovaccines for antigen and adjuvant codelivery: an in vitro and in vivo comparison
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SYSNO ASEP 0584374 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název pH and ROS responsiveness of polymersome nanovaccines for antigen and adjuvant codelivery: an in vitro and in vivo comparison Tvůrce(i) Jäger, Eliezer (UMCH-V) ORCID, RID
Ilina, O. (NL)
Dölen, Y. (NL)
Valente, M. (NL)
van Dinther, E. A. W. (NL)
Jäger, Alessandro (UMCH-V) RID, ORCID
Figdor, C. G. (NL)
Verdoes, M. (NL)Zdroj.dok. Biomacromolecules. - : American Chemical Society - ISSN 1525-7797
Roč. 25, č. 3 (2024), s. 1749-1758Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova vaccine ; dendritic cells ; antigens Vědní obor RIV CD - Makromolekulární chemie Obor OECD Polymer science CEP LM2023053 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy GJ20-15077Y GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora UMCH-V - RVO:61389013 UT WOS 001162206300001 EID SCOPUS 85183516419 DOI 10.1021/acs.biomac.3c01235 Anotace The antitumor immunity can be enhanced through the synchronized codelivery of antigens and immunostimulatory adjuvants to antigen-presenting cells, particularly dendritic cells (DCs), using nanovaccines (NVs). To study the influence of intracellular vaccine cargo release kinetics on the T cell activating capacities of DCs, we compared stimuli-responsive to nonresponsive polymersome NVs. To do so, we employed “AND gate” multiresponsive (MR) amphiphilic block copolymers that decompose only in response to the combination of chemical cues present in the environment of the intracellular compartments in antigen cross-presenting DCs: low pH and high reactive oxygen species (ROS) levels. After being unmasked by ROS, pH-responsive side chains are exposed and can undergo a charge shift within a relevant pH window of the intracellular compartments in antigen cross-presenting DCs. NVs containing the model antigen Ovalbumin (OVA) and the iNKT cell activating adjuvant α-Galactosylceramide (α-Galcer) were fabricated using microfluidics self-assembly. The MR NVs outperformed the nonresponsive NV in vitro, inducing enhanced classical- and cross-presentation of the OVA by DCs, effectively activating CD8+, CD4+ T cells, and iNKT cells. Interestingly, in vivo, the nonresponsive NVs outperformed the responsive vaccines. These differences in polymersome vaccine performance are likely linked to the kinetics of cargo release, highlighting the crucial chemical requirements for successful cancer nanovaccines. Pracoviště Ústav makromolekulární chemie Kontakt Eva Čechová, cechova@imc.cas.cz ; Tel.: 296 809 358 Rok sběru 2025 Elektronická adresa https://pubs.acs.org/doi/10.1021/acs.biomac.3c01235
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