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利用超声触发的透明质酸偶联脂质体靶向治疗乳腺癌。

Targeting Breast Cancer Using Hyaluronic Acid-Conjugated Liposomes Triggered with Ultrasound.

出版信息

J Biomed Nanotechnol. 2021 Jan 1;17(1):90-99. doi: 10.1166/jbn.2021.3012.

DOI:10.1166/jbn.2021.3012
PMID:33653499
Abstract

The successful targeting of tumors can be achieved by conjugating targeting moieties to nanoparticles. These modifications allow nannocarriers to achieve greater targeting specificity through binding to specific receptors overexpressed on the surface of the tumor cells. In this study, pegylated liposomes encapsulating the model drug/dye calcein and conjugated to hyaluronic acid (HA) molecules were successfully synthesized, and their ability to target HA receptors overexpressed on a breast cancer cell line was investigated . Low-frequency ultrasound (LFUS), applied at three different power densities (6.2, 9, and 10 mW/cm²) were used to trigger the release of the entrapped calcein. Both the control and HAconjugated liposomes showed similar release profiles. HA conjugation to the liposomes resulted in a significant increase in calcein uptake by the breast cancer cell line MDA-MB-231 known for its CD44 (HA receptor) overexpression, while such an effect was not recorded with NIH-3T3, an embryonic mouse fibroblast, with low levels of CD44 expression. The application of low LFUS showed a significant enhancement of calcein uptake by MDA-MB-231 cells from our liposome compared to calcein uptake without cell exposure to ultrasound. These findings suggest that combining HA-conjugated liposomes with ultrasound is a promising drug delivery platform in breast cancer treatment.

摘要

通过将靶向部分与纳米颗粒缀合,可以实现肿瘤的靶向治疗。这些修饰使纳米载体能够通过与肿瘤细胞表面过表达的特定受体结合,实现更高的靶向特异性。在这项研究中,成功合成了包裹模型药物/染料钙黄绿素的聚乙二醇化脂质体,并与透明质酸(HA)分子缀合,研究了它们靶向在乳腺癌细胞系上过表达的 HA 受体的能力。低频超声(LFUS)以三种不同的功率密度(6.2、9 和 10 mW/cm²)应用于触发包封的钙黄绿素的释放。对照和 HA 缀合的脂质体均表现出相似的释放曲线。HA 与脂质体的缀合导致乳腺癌细胞系 MDA-MB-231(因其过表达 CD44(HA 受体)而闻名)对钙黄绿素的摄取显著增加,而在 NIH-3T3(一种低表达 CD44 的胚胎小鼠成纤维细胞)中未记录到这种作用。与未暴露于超声的细胞相比,应用 LFUS 可显著增强 MDA-MB-231 细胞从我们的脂质体中摄取钙黄绿素。这些发现表明,将 HA 缀合的脂质体与超声结合是治疗乳腺癌的一种很有前途的药物传递平台。

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