Premium
Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response
Author(s) -
Kim SunYoung,
Heo Min Beom,
Hwang GeumSook,
Jung Youngae,
Choi Do Yeol,
Park YeongMin,
Lim Yong Taik
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201501380
Subject(s) - tlr9 , endosome , chemistry , immune system , in vivo , in vitro , microbiology and biotechnology , biophysics , receptor , biochemistry , biology , immunology , gene , gene expression , dna methylation
We have designed and synthesized linear polymer‐based 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 HA‐CpG 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.