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CD44-Tropic Polymeric Nanocarrier for Breast Cancer Targeted Rapamycin Chemotherapy
Zhao, Yunqi Zhang, Ti Duan, Shaofeng Davies, Neal M. Forrest, M. Laird
Zhao, Yunqi
Zhang, Ti
Duan, Shaofeng
Davies, Neal M.
Forrest, M. Laird
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Abstract
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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2014-08
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Future Medicine
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Forrest_2014.pdf
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Keywords
Hyaluronic acid, Rapamycin, CD44, Breast Cancer
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