Journal
JOURNAL OF MATERIALS CHEMISTRY B
Volume 1, Issue 41, Pages 5686-5693Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c3tb20906g
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Funding
- National Research Foundation of Korea (NRF)
- Ministry of Education Science & Technology (MEST) [2010-0019923, 2012-2043991]
- Bio & Medical Technology Development Program of NRF
- Korean government (MEST) [2012050077]
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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 pi-hyaluronan nanocarrier (pi HNC) for CD44-targeted and pH-boosted delivery of an aromatic anticancer drug to cancer cells. Amphiphilic pi-hyaluronan (pyrenyl hyaluronan, pi HA) was synthesized using EDC chemistry, and self-assembled to form pi HNC, the structure of which was obviously micellar but was convincingly effective to function; (i) a pi-rich pyrenyl core of pi HNC, a loading aromatic drug (doxorubicin, DOX) by pi-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 pi HNC acted as a ligand for CD44 resulting in the localization of pi HNC 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 pi HNC (pi HNC/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.
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