title: Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response.
abstract: 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.
authors.affiliation: SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (Republic of Korea).
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (Republic of Korea).
authors.forename: Min Beom
authors.initials: MB
authors.lastname: Heo
authors.affiliation: Koreas Basic Science Institute (Republic of Korea).
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
authors.affiliation: Koreas Basic Science Institute (Republic of Korea).
authors.forename: Youngae
authors.initials: Y
authors.lastname: Jung
authors.affiliation: SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (Republic of Korea).
authors.forename: Do Yeol
authors.initials: DY
authors.lastname: Choi
authors.affiliation: Konkuk University (Republic of Korea). immun3023@kku.ac.kr.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (Republic of Korea). yongtaik@skku.edu.
authors.forename: Yong Taik
authors.initials: YT
authors.lastname: Lim
mesh_terms: D045744:Cell Line, Tumor; D011992:Endosomes / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*
chemical_list: D011108:Polymers
keywords: cancer therapy; immune cells; immunity; multivalent ligands; nanocomplexes