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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Multivalent Polymer Nanocomplex Targeting Endosomal Receptor of Immune Cells for Enhanced Antitumor and Systemic
Sun-Young Kim1, Min Beom Heo1, Geum-Sook Hwang2
1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon (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.
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