期刊
JOURNAL OF COLLOID AND INTERFACE SCIENCE
卷 611, 期 -, 页码 129-136出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jcis.2021.12.054
关键词
Sulfavants; Colloid; Aggregates; Fluorescence; cryo-TEM; Biological activity; Immune response
资金
- project Antitumor Drugs and Vaccines from the Sea (ADViSE) project - POR Campania FESR 20142020 Technology Platform for Therapeutic Strategies against Cancer -Action 1.1.2 and 1.2.2. [CUP B43D18000240007 -SURF 17061BP000000011]
This study investigates the chemical characteristics and self-assembly behavior of Sulfavant A and Sulfavant R, two potential vaccine adjuvants. The results demonstrate that the formation and stability of their aggregates vary with concentration, which in turn affects their immunomodulatory abilities.
Sulfavant A and Sulfavant R, sulfoquinovoside-glycerol lipids under study as vaccine adjuvants, structurally differ only for the configuration of glyceridic carbon, R/S and R respectively. The in vitro activity of these substances follows a bell-shaped dose-response curve, but Sulfavant A gave the best response around 20 mM, while Sulfavant R at 10 nM. Characterization of aqueous self-assembly of these molecules by a multi-technique approach clarified the divergent and controversial biological outcome. Supramolecular structures were present at concentrations much lower than critical aggregation concentration for both products. The kind and size of these aggregates varied as a function of the concentration differently for Sulfavant A and Sulfavant R. At nanomolar range, Sulfavant A formed cohesive vesicles, while Sulfavant R arranged in spherical micellar particles whose reduced stability was probably responsible for an increase of monomer concentration in accordance with immunomodulatory profile. Instead, at micromolar concentrations transition from micellar to vesicular state of Sulfavant R occurred and thermodynamic stability of the aggregates, assessed by surface tensiometry, correlated with the bioactivity of Sulfavant A at 20 mM and the complete loss of efficacy of Sulfavant R. The study of Sulfavants provides clear evidence of how self-aggregation, often neglected, and the equilibria between monomers and aqueous supramolecular forms of lipophilic molecules deeply determine the overall bio-response. (C) 2021 Elsevier Inc. All rights reserved.
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