Facile One-Pot Preparation of Self-Assembled Hyaluronate/Doxorubicin Nanoaggregates for Cancer Therapy.

IF 3.4 3区 医学 Q1 ENGINEERING, MULTIDISCIPLINARY
Yong Geun Lim, Hyung Geun Park, Kyeongsoon Park
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Abstract

Hyaluronic acid (HA)-based delivery systems for doxorubicin (DOX) have been developed to selectively target cancer cells and enhance their therapeutic effects while reducing systemic side effects. However, conventional methods for preparing HA-based drug delivery systems are often limited by multistep synthetic processes, time-consuming purification, and the use of crosslinkers or surfactants, which can cause undesired toxicities. To resolve these issues, we developed a facile one-pot method to prepare self-assembled sodium hyaluronate/doxorubicin (HA/DOX) nanoaggregates by mixing HA and DOX. The self-assembled HA/DOX nanoaggregates were formed via cation-π interactions between the aromatic moiety of DOX and Na+ ions in HA as well as electrostatic interactions between HA and DOX. The optimized HA/DOX nanoaggregates with a [DOX]/[HA] molar ratio of 5 had an average particle size of approximately 250 nm and a sphere-like shape. In vitro studies revealed that HA/DOX nanoaggregates effectively targeted CD44-overexpressing cancer cells, selectively delivering DOX into the cell nuclei more efficiently than free DOX and resulting in enhanced cytotoxic effects. Annexin V and transferase dUTP nick-end labeling assays confirmed that HA/DOX nanoaggregates induced apoptosis via DNA fragmentation more effectively than free DOX.

一锅制备自组装透明质酸/阿霉素纳米聚集体用于癌症治疗。
基于透明质酸(HA)的多柔比星(DOX)递送系统已经被开发出来,可以选择性地靶向癌细胞,增强其治疗效果,同时减少全身副作用。然而,制备ha基药物传递系统的传统方法通常受到多步骤合成过程、耗时的纯化以及使用交联剂或表面活性剂的限制,这可能导致意想不到的毒性。为了解决这些问题,我们开发了一种简单的一锅法,通过混合透明质酸钠和DOX来制备自组装透明质酸钠/阿霉素(HA/DOX)纳米聚集体。自组装的HA/DOX纳米聚集体是通过HA中DOX的芳香部分与Na+离子之间的阳离子-π相互作用以及HA与DOX之间的静电相互作用形成的。优化后的[DOX]/[HA]摩尔比为5的HA/DOX纳米聚集体平均粒径约为250 nm,呈球形。体外研究表明,HA/DOX纳米聚集体可以有效靶向cd44过表达的癌细胞,比游离DOX更有效地选择性地将DOX传递到细胞核中,从而增强细胞毒性作用。膜联蛋白V和转移酶dUTP镍端标记实验证实,HA/DOX纳米聚集体比游离DOX更有效地通过DNA片段诱导细胞凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomimetics
Biomimetics Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
3.50
自引率
11.10%
发文量
189
审稿时长
11 weeks
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