Qiao Jia-Xin, Guo Dong-Yan, Tian Huan, Wang Zhan-Peng, Fan Qiang-Qiang, Tian Yuan, Sun Jing, Zhang Xiao-Fei, Zou Jun-Bo, Cheng Jiang-Xue, Luan Fei, Zhai Bing-Tao
State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research, Shaanxi University of Chinese Medicine, Xi'an, 712046, China.
Department of Pharmacy, National Old Pharmacist Inheritance Studio, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, 710021, China.
Mater Today Bio. 2024 Nov 23;29:101358. doi: 10.1016/j.mtbio.2024.101358. eCollection 2024 Dec.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the loss or low expression of estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2) and progesterone receptor (PR). Due to the lack of clear therapeutic targets, paclitaxel (PTX) is often used as a first-line standard chemotherapy drug for the treatment of high-risk and locally advanced TNBC. PTX is a diterpenoid alkaloid extracted and purified from Taxus plants, functioning as an anticancer agent by inducing and promoting tubulin polymerization, inhibiting spindle formation in cancer cells, and preventing mitosis. However, its clinical application is limited by low solubility and high toxicity. Nanodrug delivery system (NDDS) is one of the feasible methods to improve the water solubility of PTX and reduce side effects. In this review, we summarize the latest advancements in PTX-targeted NDDS, as well as its combination with other codelivery therapies for TNBC treatment. NDDS includes passive targeting, active targeting, stimuli-responsive, codelivery, and multimode strategies. These systems have good prospects in improving the bioavailability of PTX, enhancing tumor targeting, reducing toxicity, controlling drug release, and reverse tumor multidrug resistance (MDR). This review provides valuable insights into the clinical development and application of PTX-targeted NDDS in the treatment of TNBC.
三阴性乳腺癌(TNBC)是乳腺癌中最具侵袭性的亚型,其特征是雌激素受体(ER)、人表皮生长因子受体2(HER2)和孕激素受体(PR)缺失或低表达。由于缺乏明确的治疗靶点,紫杉醇(PTX)常被用作治疗高危和局部晚期TNBC的一线标准化疗药物。PTX是从红豆杉植物中提取纯化的二萜生物碱,通过诱导和促进微管蛋白聚合、抑制癌细胞纺锤体形成以及阻止有丝分裂发挥抗癌作用。然而,其临床应用受到低溶解度和高毒性的限制。纳米药物递送系统(NDDS)是提高PTX水溶性并减少副作用的可行方法之一。在本综述中,我们总结了PTX靶向NDDS的最新进展,以及其与其他共递送疗法联合用于TNBC治疗的情况。NDDS包括被动靶向、主动靶向、刺激响应、共递送和多模式策略。这些系统在提高PTX的生物利用度、增强肿瘤靶向性、降低毒性、控制药物释放以及逆转肿瘤多药耐药(MDR)方面具有良好前景。本综述为PTX靶向NDDS在TNBC治疗中的临床开发和应用提供了有价值的见解。