通过基于循环德克斯特林/马尔托基因氨基酶的酶介导控制释放系统增强多塞塔塞尔的向性细胞毒性和亡作用
Zahra Sattari1, Simin Dadashzadeh2, Soraya Shahhosseini3
1Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-154, Iran.
International journal of pharmaceutics
|March 29, 2025
概括
使用多塞塔克塞尔 (DTX) 和前列腺特异性膜抗原 (PSMA) 连接体的新向药物递送系统显示,前列腺癌治疗得到改善. 这种系统增强了药物的疗效,并通过专门向癌细胞来减少副作用.
科学领域:
- 生物结合化学 生物结合化学
- 纳米医学是一种纳米医学.
- 癌症治疗方法 癌症治疗方法
背景情况:
- 前列腺癌仍然是一个重大的健康问题,需要改进治疗策略.
- 多赛 (DTX) 是一种有效的抗癌药物,但具有不良的溶解性和全身毒性.
- 前列腺特异性膜抗原 (PSMA) 是前列腺癌诊断和治疗的验证标.
研究的目的:
- 开发一种新的针对性药物输送系统,用于dcetaxel (DTX) 使用PSMA向带.
- 为了增强DTX对表达PSMA的前列腺癌细胞的治疗疗效.
- 评估开发的向输送系统的体外性能和细胞毒性.
主要方法:
- 马尔托基性粉酶 (MAase) 与氨酸-尿素-氨酸 (EUK) 仿真的结合,以PSMA为点,由德克斯促进.
- 使用UV-vis和FT-IR光谱学制备和表征β-环氧德克斯 (β-CD) -DTX纳入复合物.
- 在体外细胞毒性测定 (IC50测定) 和流式细胞计分析LNCaP细胞中诱导亡的分析.
主要成果:
- 与非向系统 (IC50 = 60 nM) 相比,β-CD-DTX/MAase-EUK生物结合体对PSMA阳性LNCaP细胞显著增强细胞毒性 (IC50 = 34 nM).
- 生物结合物显著增加了LNCaP细胞的早期 (28.2%) 和晚期 (14.2%) 亡率.
- 用生物结合物治疗导致LNCaP细胞中caspase-3/7的激活增加.
结论:
- 这种新的有针对性的输送系统有效地提高了DTX的溶解性和生物可用性.
- 针对PSMA的生物结合物通过选择性向癌细胞来提高治疗前列腺癌的疗效.
- 这种方法有望缓解全身毒性并改善前列腺癌患者的治疗结果.
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