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纳米颗粒靶向 CD44 阳性癌细胞用于前列腺癌治疗中的靶向药物递送。

Nanoparticle Targeting CD44-Positive Cancer Cells for Site-Specific Drug Delivery in Prostate Cancer Therapy.

机构信息

Department of Applied Cosmetology, Master Program of Cosmetic Science, Hung-Kuang University , Taichung 43302, Taiwan.

Department of Biological Science and Technology, China Medical University , Taichung 40402, Taiwan.

出版信息

ACS Appl Mater Interfaces. 2016 Nov 16;8(45):30722-30734. doi: 10.1021/acsami.6b10029. Epub 2016 Nov 7.

Abstract

Prostate cancer is one of the leading causes of cancer death in adult men and is a multistage disease with therapeutic challenges of local recurrent advanced tumors and distant metastatic disease. CD44 is a multifunctional and multistructural cell surface glycoprotein that is involved in cell-cell interactions, cell proliferation, and cell migration. In the study, we produced negatively charged and biocompatible hyaluronic acid-based nanoparticles as a therapeutic system for targeting CD44-positive cancer cells. Subsequently, we confirmed the delivery of bioactive epigallocatechin-3-gallate and site-specific inhibition of prostate tumor growth. In this study, hyaluronic acid-based nanoparticles successfully encapsulated epigallocatechin-3-gallate and were efficiently internalized into cancer cells via CD44 ligand receptor recognition, induced cell cycle arrest at G2/M phase, and inhibited prostate cancer cell growth. Furthermore, in vivo assays indicated that these nanoparticles specifically bind CD44 receptors and increase apoptosis of cancer cells, leading to significant decreases in prostate tumor activity and tumor tissue inflammation.

摘要

前列腺癌是成年男性癌症死亡的主要原因之一,是一种多阶段疾病,具有局部复发性晚期肿瘤和远处转移性疾病的治疗挑战。CD44 是一种多功能和多结构的细胞表面糖蛋白,参与细胞-细胞相互作用、细胞增殖和细胞迁移。在这项研究中,我们制备了带负电荷且生物相容的透明质酸基纳米颗粒作为针对 CD44 阳性癌细胞的治疗系统。随后,我们证实了生物活性表没食子儿茶素没食子酸酯的递送和前列腺肿瘤生长的位点特异性抑制。在这项研究中,透明质酸基纳米颗粒成功地包封了表没食子儿茶素没食子酸酯,并通过 CD44 配体受体识别有效地被内化到癌细胞中,诱导细胞周期停滞在 G2/M 期,并抑制前列腺癌细胞生长。此外,体内实验表明,这些纳米颗粒特异性结合 CD44 受体并增加癌细胞凋亡,导致前列腺肿瘤活性和肿瘤组织炎症显著降低。

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