齐墩果酸是天然产物中的活性成分，具有抗乳腺癌活性。但其水溶性差、生物利用度低限制了其在临床上的有效性。为了提高齐墩果酸的抗癌活性，我们合成了一种新型齐墩果酸季铵（QDT），在静电相互作用的驱动下，将其引入肝素中并涂覆壳聚糖，得到QDT/肝素/壳聚糖纳米聚集体（QDT/HEP/CS不适用）。 QDT/HEP/CS NAs 显示负 zeta 电位 (-35.01 ± 4.38 mV)、合适的条形平均粒径 (150.45 ± 0.68 nm) 和高载药量 (36%)。包覆壳聚糖在生理条件下对QDT具有较强的抗渗漏特性。更重要的是，QDT在肿瘤细胞中持续释放后，可以显着降低线粒体膜电位并诱导乳腺癌细胞凋亡。对 4 T1 荷瘤小鼠的进一步体内抗肿瘤研究证实，QDT/HEP/CS NA 通过上调 caspase-3、caspase-9 和细胞色素 C 来增强抗癌功​​效，这归因于通过增强的渗透性和保留作用。此外，QDT/HEP/CS NA 显着增强了 QDT 的体外和体内生物安全性和生物相容性。总的来说，开发具有高抗肿瘤活性、良好的生物分布和良好的生物相容性的QDT/HEP/CS NAs，为提高中药成分的抗癌效果提供了一种安全、简便、有前景的策略。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Oleanolic acid is an active ingredient from natural products with anti-breast cancer activity. However, the poor solubility in water and low bioavailability have limited its effectiveness in clinic. To improve the anticancer activity of oleanolic acid, we synthesized a novel oleanolic quaternary ammonium (QDT), which, driven by electrostatic interactions, was introduced into heparin and coated with chitosan to obtain a QDT/heparin/chitosan nanoaggregate (QDT/HEP/CS NAs). QDT/HEP/CS NAs showed the negative zeta potential (-35.01 ± 4.38 mV), suitable mean particle size (150.45 ± 0.68 nm) with strip shape, and high drug loading (36 %). The coated chitosan had strong anti-leakage characteristics toward QDT under physiological conditions. More importantly, upon sustained release in tumor cells, QDT could significantly decrease the mitochondrial membrane potential and induce apoptosis of breast cancer cells. Further in vivo antitumor study on 4 T1 tumor-bearing mice confirmed the enhanced anticancer efficacy of QDT/HEP/CS NAs via upregulation of caspase-3, caspase-9 and cytochrome C, which was attributed to the high accumulation in tumor via the enhanced permeability and retention effect. Moreover, QDT/HEP/CS NAs significantly enhanced the biosafety and biocompatibility of QDT in vitro and in vivo. Collectively, the development of QDT/HEP/CS NAs with high antitumor activity, favorable biodistribution and good biocompatibility provided a safe, facile and promising strategy to improve the anti-cancer effect of traditional Chinese medicine ingredients.Copyright © 2024 Elsevier B.V. All rights reserved.