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Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic Memory Response
Authors:Sun‐Young Kim  Min Beom Heo  Dr. Geum‐Sook Hwang  Youngae Jung  Dr. Do Yeol Choi  Prof. Dr. Yeong‐Min Park  Prof. Dr. Yong Taik Lim
Affiliation:1. SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (Republic of Korea);2. Koreas Basic Science Institute (Republic of Korea);3. Konkuk University (Republic of Korea)
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.
Keywords:cancer therapy  immune cells  immunity  multivalent ligands  nanocomplexes
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