π-Hyaluronan nanocarriers for CD44-targeted and pH-boosted aromatic drug delivery

Eunji Jang, Eun Kyung Lim, Yuna Choi, Eunjung Kim, Hyun Ouk Kim, Dong Joo Kim, Jin Suck Suh, Yong Min Huh, Seungjoo Haam

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Molecular targeted delivery of therapeutic agents and their stimuli-responsive release are some of the major issues for modern medical administration, particularly in cancer chemotherapy. In this study, we developed a π-hyaluronan nanocarrier (πHNC) for CD44-targeted and pH-boosted delivery of an aromatic anticancer drug to cancer cells. Amphiphilic π-hyaluronan (pyrenyl hyaluronan, πHA) was synthesized using EDC chemistry, and self-assembled to form πHNC, the structure of which was obviously micellar but was convincingly effective to function; (i) a π-rich pyrenyl core of πHNC, a loading aromatic drug (doxorubicin, DOX) by π-stacking attraction, showed a rapid release profile under low pH conditions which is a notable characteristic of the cancer microenvironment as well as the endolysosomal state after uptake into the target cell and (ii) the hydrophilic hyaluronan shell of πHNC acted as a ligand for CD44 resulting in the localization of πHNC into the target cell by CD44-mediated endocytosis, without cytotoxicity. With its targeted and stimulated delivery of aromatic drugs to the target cells, DOX-loaded πHNC (πHNC/DOX) provided effectual therapeutic activity in both in vitro and in vivo models of CD44-positive human gastric cancer, which is suitable as a facile and efficient drug delivery platform.

Original languageEnglish
Pages (from-to)5686-5693
Number of pages8
JournalJournal of Materials Chemistry B
Volume1
Issue number41
DOIs
Publication statusPublished - 2013 Nov 7

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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