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靶向 CD44 的透明质酸包覆的拉帕替尼纳米晶体增强了对三阴性乳腺癌的疗效。

CD44 targeting hyaluronic acid coated lapatinib nanocrystals foster the efficacy against triple-negative breast cancer.

机构信息

Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, India; Academy of Scientific and Innovative Research (AcSIR), Chennai, TN, India.

Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, India.

出版信息

Nanomedicine. 2018 Feb;14(2):327-337. doi: 10.1016/j.nano.2017.10.010. Epub 2017 Nov 9.

Abstract

Lapatinib (LPT) is an orally administered drug for the treatment of metastatic breast cancer. For expanding its therapeutic horizon, we have prepared its nanocrystals (LPT-NCs) that were subsequently coated with hyaluronic acid (HA) to produce LPT-HA-NCs. The detailed in-vitro and in-vivo investigation of LPT-HA-NCs showed the superior anticancer activity due to active targeting to CD44 receptors than the counterparts LPT-NCs and free LPT. In the triple negative 4T1 cells induced breast tumor bearing female Balb/C mice; LPT-HA-NCs treatment caused significant retardation of tumor growth and overall increase in animal survival probability because of their higher tumor localization, increased residence time. Our findings clearly suggest that HA coated LPT-NCs formulation enhances the activity of LPT against triple negative breast cancer. It exhibited magnificent therapeutic outcome at low dose thus presenting a strategy to reduce dose administrations and minimize dose related toxicity.

摘要

拉帕替尼(LPT)是一种用于治疗转移性乳腺癌的口服药物。为了扩大其治疗范围,我们制备了其纳米晶体(LPT-NCs),随后用透明质酸(HA)进行涂层,以产生 LPT-HA-NCs。对 LPT-HA-NCs 的详细体外和体内研究表明,由于主动靶向 CD44 受体,其抗癌活性优于 LPT-NCs 和游离 LPT。在诱导雌性 Balb/C 小鼠患有三阴性 4T1 细胞的乳腺癌肿瘤中;由于其更高的肿瘤定位和增加的滞留时间,LPT-HA-NCs 治疗导致肿瘤生长明显延迟和动物总生存概率的整体增加。我们的研究结果清楚地表明,透明质酸涂层的 LPT-NCs 制剂增强了 LPT 对三阴性乳腺癌的活性。它以低剂量表现出极好的治疗效果,因此提出了一种减少剂量给药和最小化剂量相关毒性的策略。

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