释放氧化的局部治疗皮肤黑色素瘤
Quincy E Grayton1, Heba El-Ahmad2, Anna L Lynch1
1Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Molecular pharmaceutics
|October 1, 2024
概括
氧化 (NO) 捐赠者对黑色素瘤治疗有前途,有效性取决于NO有效载荷. 大分子NO捐赠者提供有针对性的输送和对健康细胞的毒性降低,改善治疗潜力.
科学领域:
- 生物化学 生物化学
- 材料科学 材料科学 材料科学
- 皮肤病学 皮肤病学
背景情况:
- 黑色素瘤具有很高的耐药性,目前的免疫疗法等治疗方法会产生不良影响.
- 氧化 (NO) 具有抗癌性质,抗性潜力低,毒性有限,使其成为潜在的黑色素瘤治疗方法.
- 了解NO捐赠者的特征对于优化抗黑色素瘤活性至关重要.
研究的目的:
- 评估三种宏分子氧化 (NO) 供体系统的体外治疗疗效.
- 评估NO捐赠体对黑色素瘤和健康皮肤细胞的皮肤透和毒性.
- 优化一个交付系统,以提高NO捐赠者的性能.
主要方法:
- 研究了三种宏分子NO供体系统:环氧德克斯,半孔纳米颗粒和酸.
- 在实验室对黑色素瘤和健康皮肤细胞的细胞毒性进行了评估.
- 根据NO的供体大小和电荷进行了体外皮肤透的评估.
- 优化了一个Pluronic F127器官凝,用于NO供体输送.
主要成果:
- 黑色素瘤细胞细胞毒性与NO有效载荷相关,不论捐赠者类型或释放动力学.
- 根据捐赠者,健康细胞的细胞毒性有所不同;循环氨酸和氨酸的捐赠者表现出更高的治疗指数.
- 更小,中性NO捐赠者表现出更大的皮肤透.
- 提供基于环氧二烯的NO供体的器官凝增强了皮肤透率,并减少了体内瘤的生长.
结论:
- 大分子NO捐赠者可以定制用于黑色素瘤治疗,平衡有效性和安全性.
- NO 供体属性 (大小,电荷,有效载荷) 显著影响治疗结果和输送.
- 优化的输送系统,如器官凝,可以提高基于NO的黑色素瘤治疗的临床潜力.
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