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载多柔比星的功能化硒纳米颗粒用于增强宫颈癌治疗中的抗肿瘤疗效。

Doxorubicin-loaded functionalized selenium nanoparticles for enhanced antitumor efficacy in cervical carcinoma therapy.

机构信息

Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Central Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China; Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.

Central Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510120, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110100. doi: 10.1016/j.msec.2019.110100. Epub 2019 Aug 21.

Abstract

Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.

摘要

新型肿瘤靶向药物载体的开发对于癌症治疗非常重要,已成为设计纳米尺度化疗药物传递系统的主要课题之一。本研究中,采用硒纳米粒子(SeNPs)修饰透明质酸(HA)制备了透明质酸修饰的硒纳米粒子(HA-SeNPs),并将其用于负载阿霉素(DOX)以制备肿瘤靶向功能化硒纳米粒子 HA-Se@DOX。研究了 HA-Se@DOX 对人宫颈癌的体内外抗肿瘤活性。HA-Se@DOX 对宫颈癌 HeLa 细胞和人脐静脉内皮细胞(HUVEC)具有选择性的细胞摄取。体外释放结果表明,与正常生理环境相比,DOX 在酸性环境中从 HA-SeNPs 中的释放更快,在最初的 30 h 内,在 pH 值为 5.4 时,76.9%的 DOX 被释放。HA-Se@DOX 对抑制 HeLa 细胞增殖具有很高的活性,并通过激活 Bcl-2 信号通路引发 HeLa 细胞凋亡。体内抗肿瘤研究表明,HA-Se@DOX 通过抑制癌细胞增殖和诱导癌细胞凋亡来抑制肿瘤生长。有趣的是,HA-Se@DOX 在体内外的抗肿瘤活性均强于游离 DOX 和 Se@DOX。此外,在所用剂量下,HA-Se@DOX 不会对主要器官造成损伤。HA-Se@DOX 是一种很有前途的人宫颈癌治疗药物,本研究为癌症治疗提供了一种新的治疗策略。

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