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自动加载的TRAIL外体来自诱导的神经干细胞,用于脑癌治疗

Xiaopei Zhang¹, Hannah Taylor¹, Alain Valdivia¹

¹Eshelman School of Pharmacy, Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Journal of controlled release : official journal of the Controlled Release Society

|June 22, 2024

概括

来自转分化诱导的神经干细胞 (iNSCs) 的细胞外囊 (EVs) 显示出对脑癌治疗的前景. 这些工程EV有效地准和消除脑癌细胞,在临床前模型中显著提高了生存率.

科学领域:

细胞生物学细胞生物学
神经科学是一个神经科学.
在瘤学瘤学.

背景情况:

转基因分化 (TD) 提供了一种途径,可以在没有多能中间体的情况下产生专门的细胞,非常适合个性化治疗.
细胞外囊泡 (EVs) 正在成为强大的治疗输送载体.
脑癌仍然是一个重大的治疗挑战,需要新的治疗策略.

研究的目的:

研究从转分化诱导的神经干细胞 (Exo-iNSCs) 衍生出的细胞外囊作为治疗脑癌的疗效.
评估装有 TRAIL 基因产品 (Exo-iNSC-TRAIL) 的工程电动汽车的瘤向和杀死癌症的能力.

主要方法:

基因工程诱导的神经干细胞 (iNSCs) 产生装有 TRAIL 的 EV.
使用ex vivo有机型脑切片培养和共同培养试验来评估EV吸收和细胞毒性.
评估了Exo-iNSC-TRAIL在乳腺至大脑异位移植和质母细胞瘤 (U87,GBM8) 的 ортотоп性小鼠模型中的疗效.

主要成果:

与父母纤维细胞相比,工程iNSCs产生了具有显著更高 TRAIL负载的 EV.
与自由的 TRAIL 相比,exo-iNSC-TRAIL 证明了瘤焦点的选择性积累和上层癌细胞的杀死.
在体内研究表明,在接受EXO-iNSC-TRAIL治疗的小鼠中,瘤异种移植的减少约为3000倍,90天的存活率显著超过自由TRAIL.
在质母细胞瘤模型中,exo-iNSC-TRAIL还显著增加了存活率.

结论:

Exo-iNSC-TRAIL代表了一种新,稳定且易于生成的治疗大脑癌症的治疗剂.
这些工程EV提供了一个瘤向的输送系统,具有强大的抗癌活性.
这种方法对开发有效的个性化抗癌疗法来治疗大脑恶性瘤具有重大潜力.

关键词:

脑癌脑癌是一种脑癌.外基因组是外基因组的组成部分.细胞外囊泡中的细胞外囊泡.轨道的轨道是一个轨道.在NSCs中,iNSCs是最重要的.

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