Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery

Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation...

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Main Authors: Jessica L. Woodman, Min Sung Suh, Jianxing Zhang, Yuvabharath Kondaveeti, Diane J. Burgess, Bruce A. White, Glenn D. Prestwich, Liisa T. Kuhn
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Cell Biology
Online Access:http://dx.doi.org/10.1155/2015/249573
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author Jessica L. Woodman
Min Sung Suh
Jianxing Zhang
Yuvabharath Kondaveeti
Diane J. Burgess
Bruce A. White
Glenn D. Prestwich
Liisa T. Kuhn
author_facet Jessica L. Woodman
Min Sung Suh
Jianxing Zhang
Yuvabharath Kondaveeti
Diane J. Burgess
Bruce A. White
Glenn D. Prestwich
Liisa T. Kuhn
author_sort Jessica L. Woodman
collection DOAJ
description Carboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/low human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaPCMHACDDP. nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43 mV zeta potential. nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaPCMHA-AF488 was taken up by CD44+/CD24− BT-474EMT breast cancer cells within 18 hours. nCaPCMHACDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaPCMHACDDP. This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.
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spelling doaj-art-c8225d6ea2ed4cd7881d4faa5660efbd2025-02-03T06:10:57ZengWileyInternational Journal of Cell Biology1687-88761687-88842015-01-01201510.1155/2015/249573249573Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug DeliveryJessica L. Woodman0Min Sung Suh1Jianxing Zhang2Yuvabharath Kondaveeti3Diane J. Burgess4Bruce A. White5Glenn D. Prestwich6Liisa T. Kuhn7Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USADepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USADepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, USADepartment of Cell Biology, UConn Health, Farmington, CT 06030, USADepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USADepartment of Cell Biology, UConn Health, Farmington, CT 06030, USADepartment of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84108, USADepartment of Reconstructive Sciences, UConn Health, Farmington, CT 06030, USACarboxymethyl hyaluronic acid (CMHA) is a semisynthetic derivative of HA that is recognized by HA binding proteins but contains an additional carboxylic acid on some of the 6-hydroxyl groups of the N-acetyl glucosamine sugar units. These studies tested the ability of CMHA to stabilize the formation of calcium phosphate nanoparticles and evaluated their potential to target therapy resistant, CD44+/CD24−/low human breast cancer cells (BT-474EMT). CMHA stabilized particles (nCaPCMHA) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaPCMHACDDP. nCaPCMHACDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a −43 mV zeta potential. nCaPCMHACDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaPCMHACDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaPCMHA-AF488 was taken up by CD44+/CD24− BT-474EMT breast cancer cells within 18 hours. nCaPCMHACDDP was as cytotoxic as free CDDP against the BT-474EMT cells. Subcutaneous BT-474EMT tumors were more reproducibly inhibited by a near tumor dose of 2.8 mg/kg CDDP than a 7 mg/kg dose nCaPCMHACDDP. This was likely due to a lack of distribution of nCaPCMHACDDP throughout the dense tumor tissue that limited drug diffusion.http://dx.doi.org/10.1155/2015/249573
spellingShingle Jessica L. Woodman
Min Sung Suh
Jianxing Zhang
Yuvabharath Kondaveeti
Diane J. Burgess
Bruce A. White
Glenn D. Prestwich
Liisa T. Kuhn
Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
International Journal of Cell Biology
title Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
title_full Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
title_fullStr Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
title_full_unstemmed Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
title_short Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery
title_sort carboxymethyl hyaluronan stabilized nanoparticles for anticancer drug delivery
url http://dx.doi.org/10.1155/2015/249573
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