Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy

다국어 초록 (Multilingual Abstract)

<P>Tumor targetability and site-specific drug release of therapeutic nanoparticles are key factors for effective cancer therapy. In this study, poly(ethylene glycol) (PEG)-conjugated hyaluronic acid nanoparticles (P-HA-NPs) were investigated as carriers for anticancer drugs including doxorubicin and camptothecin (CPT). P-HA-NPs were internalized into cancer cells (SCC7 and MDA-MB-231) <I>via</I> receptor-mediated endocytosis, but were rarely taken up by normal fibroblasts (NIH-3T3). During <I>in vitro</I> drug release tests, P-HA-NPs rapidly released drugs when incubated with cancer cells, extracts of tumor tissues, or the enzyme Hyal-1, which is abundant in the intracellular compartments of cancer cells. CPT-loaded P-HA-NPs (CPT-P-HA-NPs) showed dose-dependent cytotoxicity to cancer cells (MDA-MB-231, SCC7, and HCT 116) and significantly lower cytotoxicity against normal fibroblasts (NIH-3T3) than free CPT. Unexpectedly, high concentrations of CPT-P-HA-NPs demonstrated greater cytotoxicity to cancer cells than free CPT. An <I>in vivo</I> biodistribution study indicated that P-HA-NPs selectively accumulated into tumor sites after systemic administration into tumor-bearing mice, primarily due to prolonged circulation in the blood and binding to a receptor (CD44) that was overexpressed on the cancer cells. In addition, when CPT-P-HA-NPs were systemically administrated into tumor-bearing mice, we saw no significant increases in tumor size for at least 35 days, implying high antitumor activity. Overall, P-HA-NPs showed promising potential as a drug carrier for cancer therapy.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2011/ancac3.2011.5.issue-11/nn202070n/production/images/medium/nn-2011-02070n_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn202070n'>ACS Electronic Supporting Info</A></P>