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由银纳米粒子触发的 lysosome 被动化增强了亚细胞向药物治疗的效果

Xueqian Wang^1,2, Shulin Zhao^1,2, Guiqian Fang^1,2

¹School of Pharmaceutical Sciences & Institute of Materia Medica, National Key Laboratory of Advanced Drug Delivery System, Medical Science and Technology Innovation Center, Key Laboratory for Biotechnology Drugs of National Health Commission, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250117, PR China. muyanling@sdfmu.edu.cn.

|April 11, 2024

概括

科学家们开发了一种新方法来克服由 lysosomal trapping 引起的耐药性. 银纳米粒子 (Ag NPs) 禁用溶酶体,增强癌症治疗中针对亚细胞药物的有效性.

科学领域:

生物化学生物化学
纳米技术纳米技术
药理学药理学是指药理学的学科.

背景情况:

针对亚细胞的药物通常会积聚在溶酶体中,导致"溶酶体陷",从而降低药物的疗效.
目前克服 lysosomal 耐药性的策略涉及修改药物结构或使用纳米材料,这可能有缺点.

研究的目的:

通过非活性化 lysosomes 引入一种新的策略来增强药物疗效.
调查银纳米颗粒 (Ag NPs) 的用于 lysosomal 无活化和克服耐药性的使用.

主要方法:

银纳米粒子 (Cy3.5@Ag NPs) 的设计是为了在溶解体中积聚.
分析了Cy3.5@AgNP对溶酶体膜透,运动和被动性的影响.
当与Cy3.5@AgNP共同化时,评估了针对亚细胞药物的疗效.

主要成果:

Cy3.5@AgNP在溶解体中成功积累,导致溶解体膜透和失活.
AgNP显著改变了溶酶体的运动性并诱导了溶酶体的被动化.
与Cy3.5@AgNP共同化显著提高了各种针对细胞下药物的治疗效率.

结论:

使用AgNP进行溶解体无活化是一种可行的策略,可以提高药物的疗效.
这种方法为克服溶酶体诱导的耐药性提供了一个有希望的治疗途径,特别是在癌症治疗中.

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Lysosomal Hydrolases

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Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...