pH and ROS responsiveness of polymersome nanovaccines for antigen and adjuvant codelivery: an in vitro and in vivo comparison

0584374 - ÚMCH 2025 RIV US eng J - Článek v odborném periodiku
Jäger, Eliezer - Ilina, O. - Dölen, Y. - Valente, M. - van Dinther, E. A. W. - Jäger, Alessandro - Figdor, C. G. - Verdoes, M.
pH and ROS responsiveness of polymersome nanovaccines for antigen and adjuvant codelivery: an in vitro and in vivo comparison.
Biomacromolecules. Roč. 25, č. 3 (2024), s. 1749-1758. ISSN 1525-7797. E-ISSN 1526-4602
Grant CEP: GA MŠMT(CZ) LM2023053; GA ČR(CZ) GJ20-15077Y
GRANT EU: European Commission(XE) 686089 - PRECIOUS
Grant ostatní: AV ČR(CZ) MSM200501602
Program: Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků
Institucionální podpora: RVO:61389013
Klíčová slova: vaccine * dendritic cells * antigens
Obor OECD: Polymer science
Impakt faktor: 6.2, rok: 2022
Způsob publikování: Open access
https://pubs.acs.org/doi/10.1021/acs.biomac.3c01235

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.
Trvalý link: https://hdl.handle.net/11104/0353395