Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy

ACS Nano. 2011 Nov 22;5(11):8591-9. doi: 10.1021/nn202070n. Epub 2011 Oct 11.


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) via receptor-mediated endocytosis, but were rarely taken up by normal fibroblasts (NIH-3T3). During in vitro 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 in vivo 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Biological Transport
  • Camptothecin / metabolism
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacokinetics
  • Humans
  • Hyaluronic Acid / chemistry*
  • Mice
  • NIH 3T3 Cells
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Drug Carriers
  • Polyethylene Glycols
  • Doxorubicin
  • Hyaluronic Acid
  • Camptothecin