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由超声触发的ROS响应性共轭聚合物纳米颗粒用于乳腺癌联合治疗中喜树碱的释放。

ROS-responsive conjugated polymer nanoparticles triggered by ultrasound for camptothecin release in breast cancer combination therapy.

作者信息

Zhang Yipiao, Tian Tian, Zeng Zhaokui, Chen Chuanpin, Wang Rongrong, Chen Suhong, Zheng Hongliang

机构信息

Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, China.

Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Huzhou, Zhejiang 313000, China.

出版信息

J Mater Chem B. 2025 Jul 16;13(28):8446-8460. doi: 10.1039/d5tb00674k.

Abstract

The treatment of breast cancer (BC) remains a major challenge. Although chemotherapy is currently the most common treatment, it is limited by high side effects. Responsive drug delivery systems (DDS) enable the controlled release of drugs, which can decrease the side effects of chemotherapy and improve efficacy. However, achieving precise delivery and targeted release of drugs is a major challenge. Here, we present ultrasound-triggered reactive oxygen species (ROS)-responsive conjugated polymer nanoparticles for combination therapy of BC. The conjugated polymer nanoparticles are candidates for the development of potential acoustic sensitizers due to their structural properties with good stability and biocompatible acoustic activation properties. In this study, sono-sensitive polymer nanoparticles (SPN) were used for spatiotemporally controlled sonodynamic therapy (SDT) and ROS-responsive chemotherapy. It was demonstrated that the SPN possessed potent acoustic-dynamic properties and could be activated by ultrasound to generate high levels of ROS, which cleaved ROS-responsive junctions, thereby facilitating the release of camptothecin. Furthermore, the SPN exhibited good long circulation properties and biocompatibility . The SPN combined with ultrasound treatment showed significant therapeutic effects in both BC cell lines and hormonal mouse models, with tumor suppression rates as high as 76.98 ± 9.09%, and no cardiotoxicity or other side effects were observed. Therefore, the present study provides a feasible strategy for designing novel controlled-release drug systems to improve the therapeutic efficacy of BC.

摘要

乳腺癌(BC)的治疗仍然是一项重大挑战。尽管化疗是目前最常见的治疗方法,但其受到高副作用的限制。响应性药物递送系统(DDS)能够实现药物的控释,这可以降低化疗的副作用并提高疗效。然而,实现药物的精确递送和靶向释放是一项重大挑战。在此,我们展示了用于乳腺癌联合治疗的超声触发活性氧(ROS)响应性共轭聚合物纳米颗粒。共轭聚合物纳米颗粒因其具有良好稳定性的结构特性和生物相容性声学激活特性,是开发潜在声学敏化剂的候选材料。在本研究中,超声敏感聚合物纳米颗粒(SPN)用于时空可控的声动力疗法(SDT)和ROS响应性化疗。结果表明,SPN具有强大的声动力特性,可以被超声激活以产生高水平的ROS,这些ROS可裂解ROS响应连接,从而促进喜树碱的释放。此外,SPN表现出良好的长循环特性和生物相容性。SPN与超声治疗相结合在乳腺癌细胞系和激素小鼠模型中均显示出显著的治疗效果,肿瘤抑制率高达76.98±9.09%,且未观察到心脏毒性或其他副作用。因此,本研究为设计新型控释药物系统以提高乳腺癌的治疗效果提供了一种可行的策略。

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