Smart Nanocarrier Based on PEGylated Hyaluronic Acid for Cancer Therapy
Citations Over TimeTop 1% of 2011 papers
Abstract
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.
Related Papers
- → Delivery of Doxorubicin Using Double-Layered Core–Shell Nanocarrier Based on Magnetic Fe3O4 Core and Salep Shells(2018)20 cited
- → The emergence of nanocarriers in the management of diseases and disorders(2023)5 cited
- → General justification in terms of effectiveness and toxicities for the use of nanocarriers(2023)3 cited
- → Strategies for ligand-installed nanocarriers(2021)2 cited
- [Effects of cu2+ on biosynthesis of camptothecin in cell cultures of Camptotheca acuminata].(2006)