Carboxymethyl Hyaluronan-Stabilized Nanoparticles for Anticancer Drug Delivery.

Q3 Biochemistry, Genetics and Molecular Biology International Journal of Cell Biology Pub Date : 2015-01-01 Epub Date: 2015-09-10 DOI:10.1155/2015/249573
Jessica L Woodman, Min Sung Suh, Jianxing Zhang, Yuvabharath Kondaveeti, Diane J Burgess, Bruce A White, Glenn D Prestwich, Liisa T Kuhn
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引用次数: 12

Abstract

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 (nCaP(CMHA)) were loaded with the chemotherapy drug cis-diamminedichloroplatinum(II) (CDDP) to form nCaP(CMHA)CDDP. nCaP(CMHA)CDDP was determined to be poorly crystalline hydroxyapatite, 200 nm in diameter with a -43 mV zeta potential. nCaP(CMHA)CDDP exhibited a two-day burst release of CDDP that tapered resulting in 86% release by 7 days. Surface plasmon resonance showed that nCaP(CMHA)CDDP binds to CD44, but less effectively than CMHA or hyaluronan. nCaP(CMHA-AF488) was taken up by CD44(+)/CD24(-) BT-474EMT breast cancer cells within 18 hours. nCaP(CMHA)CDDP 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 nCaP(CMHA)CDDP. This was likely due to a lack of distribution of nCaP(CMHA)CDDP throughout the dense tumor tissue that limited drug diffusion.

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用于抗癌药物递送的羧甲基透明质酸稳定纳米颗粒。
羧甲基透明质酸(CMHA)是透明质酸的半合成衍生物,可被透明质酸结合蛋白识别,但在n -乙酰氨基葡萄糖糖单位的某些6-羟基上含有额外的羧酸。这些研究测试了CMHA稳定磷酸钙纳米颗粒形成的能力,并评估了它们靶向治疗耐药的CD44(+)/CD24(-/低)人乳腺癌细胞(BT-474EMT)的潜力。将CMHA稳定粒子(nCaP(CMHA))装载化疗药物顺式二胺二氯铂(CDDP),形成nCaP(CMHA)CDDP。nCaP(CMHA)CDDP为差晶羟基磷灰石,直径200 nm, zeta电位-43 mV。nCaP(CMHA)CDDP表现出2天的爆发性释放,7天后逐渐减少,释放量为86%。表面等离子体共振显示,nCaP(CMHA)CDDP与CD44结合,但效果不如CMHA或透明质酸。nCaP(CMHA-AF488)在18小时内被CD44(+)/CD24(-) BT-474EMT乳腺癌细胞摄取。nCaP(CMHA)CDDP对BT-474EMT细胞的细胞毒性与游离CDDP相同。皮下BT-474EMT肿瘤被肿瘤附近剂量2.8 mg/kg的CDDP比7 mg/kg剂量的nCaP(CMHA)CDDP更具可重复性。这可能是由于nCaP(CMHA)CDDP在整个致密肿瘤组织中缺乏分布,限制了药物扩散。
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来源期刊
International Journal of Cell Biology
International Journal of Cell Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
3.30
自引率
0.00%
发文量
4
审稿时长
20 weeks
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