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- Title
Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response.
- Authors
Sun-Young Kim; Min Beom Heo; Geum-Sook Hwang; Youngae Jung; Do Yeol Choi; Yeong-Min Park; Yong Taik Lim
- Abstract
We have designed and synthesized linear polymerbased nanoconjugates and nanocomplexes bearing multivalent immunostimulatory ligands and also demonstrated that the synthetic multivalent nanocomplexes led to an enhanced stimulation of immune cells in vitro and antitumor and systemic immune memory response in vivo. We have developed hyaluronic acid (HA)-based multivalent nanoconjugates and nanocomplexes for enhanced immunostimulation through the combination of multivalent immune adjuvants with CpG ODNs (as a TLR9 ligand) and cationic poly(l-lysine) (PLL; for the enhancement of cellular uptake). The multivalent HACpG nanoconjugate efficiently stimulated the antigen-presenting cells and the multivalent PLL/HA-CpG nanocomplex also led to an enhanced cellular uptake as well as continuous stimulation of endosomal TLR9. The mice vaccinated with dendritic cells treated with the multivalent nanocomplex exhibited tumor growth inhibition as well as a strong antitumor memory response.
- Subjects
IMMUNE response; SYSTEMIC memory hypothesis; IMMUNOLOGICAL adjuvants; LIGANDS (Chemistry); HYALURONIC acid; ANTIGENS; LABORATORY mice
- Publication
Angewandte Chemie International Edition, 2015, Vol 54, Issue 28, p8139
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201501380