CD44-Tropic Polymeric Nanocarrier for Breast Cancer Targeted Rapamycin Chemotherapy
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Issue Date
2014-08Author
Zhao, Yunqi
Zhang, Ti
Duan, Shaofeng
Davies, Neal M.
Forrest, M. Laird
Publisher
Future Medicine
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Metadata
Show full item recordAbstract
In contrast with the conventional targeting of nanoparticles to cancer cells with antibody or peptide conjugates, a hyaluronic acid (HA) matrix nanoparticle with intrinsic-CD44-tropism was developed to deliver rapamycin for localized CD44-positive breast cancer treatment. Rapamycin was chemically conjugated to the particle surface via a novel sustained-release linker, 3-amino-4-methoxy-benzoic acid. The release of the drug from the HA nanoparticle was improved by 42-fold compared to HA-temsirolimus in buffered saline. In CD44 positive MDA-MB-468 cells, using HA as drug delivery carrier, the cell-viability was significantly decreased compared to free rapamycin and CD44-blocked controls. Rat pharmacokinetics showed that the area-under-the-curve of HA nanoparticle formulation was 2.96-fold greater than that of the free drug, and the concomitant total body clearance was 8.82-fold slower. Moreover, in immunocompetent BALB/c mice bearing CD44-positive 4T1.2neu breast cancer, the rapamycin1loaded HA particles significantly improved animal survival, suppressed tumor growth and reduced the prevalence of lung metastasis.
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Citation
Zhao, Y., Zhang, T., Duan, S., Davies, N. M., & Forrest, M. L. (2014). CD44-Tropic Polymeric Nanocarrier for Breast Cancer Targeted Rapamycin Chemotherapy. Nanomedicine : Nanotechnology, Biology, and Medicine, 10(6), 1221–1230. http://doi.org/10.1016/j.nano.2014.02.015
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