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向黑色素瘤治疗:使用R8-PEI可溶性微针进行高效siRNA输送

Yaozhen He¹, Songsen Chen², Wenyang Song²

¹Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006 Guangdong, China; Guangdong High Education Institutes Engineering Research Center of Modified-released Pharmaceutical Products, Center for New Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006 Guangdong, China.

International journal of pharmaceutics

|March 26, 2025

概括

研究人员开发了装有siRNA (小干扰RNA) 和基修饰载体的可溶性微针,用于有效的皮肤黑色素瘤治疗. 这个系统增强了通过皮肤传递,抑制瘤生长和基因表达,用于潜在的新疗法.

科学领域:

生物医学工程生物医学工程
皮肤病学皮肤病学
在瘤学瘤学.

背景情况:

皮肤黑色素瘤是一种具有高转移率的致命皮肤癌.
使用小干扰RNAs (siRNAs) 的RNA干扰 (RNAi) 显示了黑色素瘤的治疗前景.
有效的siRNA传递受到降解,有限的吸收和皮肤屏障的挑战.

研究的目的:

开发一种针对皮肤黑色素瘤的siRNA的新型通过皮肤传递系统.
为了创建可溶解的微针 (DMN),载有与修饰载体 (R8-PEI) 复合的siRNA.
评估该系统在黑色素瘤治疗中的有效性和安全性.

主要方法:

制造可溶解的微针 (DMN) 装载有siRNA复合的聚乙烯胺 (PEI) 修饰的八度氨酸 (R8).
评估DMN的物理特性,机械强度和穿透皮肤的能力 (Parafilm®M和老鼠皮肤).
在体外评估siRNA@R8-PEI对A375黑色素瘤细胞 (增殖,迁移,基因沉默) 的疗效,以及在体内研究瘤载体模型.

主要成果:

siRNA@R8-PEI/DMNs表现出良好的外观,高针含量和强大的机械强度.
微针可以有效地穿透皮肤 (>80%的老鼠皮肤穿孔率).
试验室研究显示,细胞增殖有显著抑制 (~90%),迁移减少 (~20%),和高基因沉默 (~74%). 在体内研究中实现了~67%的瘤体积抑制,诱导了亡并减少了BRAF的表达.

结论:

siRNA@R8-PEI/DMNs代表了皮肤黑色素瘤治疗的有前途的通过皮肤递送系统.
开发的系统克服了皮肤癌治疗siRNA传递的关键挑战.
这种方法为在皮肤瘤学中开发安全高效的透皮siRNA载体提供了新的见解.

关键词:

细胞透的.可以溶解的微针.基因治疗是一种基因疗法.这是一种RNA干扰.siRNA的传递方式

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