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Self-assembled polymeric micelles based on hyaluronic acid-g-poly(D,L-lactide-co-glycolide) copolymer for tumor targeting.

Abstract
Graft copolymer composed hyaluronic acid (HA) and poly(D,L-lactide-co-glycolide) (PLGA) (HAgLG) was synthesized for antitumor targeting via CD44 receptor of tumor cells. The carboxylic end of PLGA was conjugated with hexamethylenediamine (HMDA) to have amine end group in the end of chain (PLGA-amine). PLGA-amine was coupled with carboxylic acid of HA. Self-assembled polymeric micelles of HAgLG have spherical morphologies and their sizes were around 50-200 nm. Doxorubicin (DOX)-incorporated polymeric micelles were prepared by dialysis procedure. DOX was released over 4 days and its release rate was accelerated by the tumoric enzyme hyaluronidase. To assess targetability of polymeric micelles, CD44-positive HepG2 cells were employed treated with fluorescein isothiocyanate (FITC)-labeled polymeric micelles. HepG2 cells strongly expressed green fluorescence at the cell membrane and cytosol. However, internalization of polymeric micelles were significantly decreased when free HA was pretreated to block the CD44 receptor. Furthermore, the CD44-specific anticancer activity of HAgLG polymeric micelles was confirmed using CD44-negative CT26 cells and CD44-positive HepG2 cells. These results indicated that polymeric micelles of HaLG polymeric micelles have targetability against CD44 receptor of tumor cells. We suggest HAgLG polymeric micelles as a promising candidate for specific drug targeting.
AuthorsGyung Mo Son, Hyun Yul Kim, Je Ho Ryu, Chong Woo Chu, Dae Hwan Kang, Su Bum Park, Young-Il Jeong
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 15 Issue 9 Pg. 16057-68 (Sep 11 2014) ISSN: 1422-0067 [Electronic] Switzerland
PMID25216338 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Hyaluronan Receptors
  • Micelles
  • Polymers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin
  • Hyaluronic Acid
  • Fluorescein-5-isothiocyanate
Topics
  • Antineoplastic Agents (pharmacology)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Doxorubicin (chemistry, pharmacology)
  • Drug Carriers (chemistry)
  • Fluorescein-5-isothiocyanate (chemistry)
  • Hep G2 Cells
  • Humans
  • Hyaluronan Receptors (metabolism)
  • Hyaluronic Acid (chemistry)
  • Lactic Acid (chemistry)
  • Micelles
  • Polyglycolic Acid (chemistry)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers (chemical synthesis, chemistry)

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