针对溶酶体进行增强癌症光动力学/光热疗法,以"一块石头两只鸟"的模式
Quanwei Sun1, Jinming Yang1, Qinghua Wu1
1School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230031, China.
ACS applied materials & interfaces
|December 20, 2023
概括
这项研究引入了一种新的纳米细胞策略,该策略结合光动力学/光热疗法 (PTT/PDT),通过免疫细胞死亡 (ICD) 和热死诱导癌细胞死亡,增强抗瘤免疫力.
科学领域:
- 生物医学工程 生物医学工程
- 癌症研究 癌症研究
- 纳米医学是一种纳米医学.
背景情况:
- 免疫性细胞死亡 (ICD) 和烧灭对于有效的癌症免疫疗法至关重要.
- 开发强大的ICD和火灭菌诱导剂是具有挑战性的,常常受到癌细胞自的阻碍.
- 光动力学/光热疗法 (PTT/PDT) 为癌症治疗提供了一种有前途的方法.
研究的目的:
- 通过将PTT/PDT与溶酶体向结合起来,开发一种用于强烈诱导ICD和热的新策略.
- 研究一种合成的二甲基二聚体 (BDPd) 基纳米细胞系统 (BDPd NPs) 对于癌症治疗的疗效.
- 在临床前癌症模型中探索 lysosomal 损伤,ICD 和 pyroptosis 诱导的协同效应.
主要方法:
- 一种化体向性二甲基二聚体 (BDPd) 的合成,具有光热和反应性氧物种 (ROS) 生成能力.
- BDPd与Pluronic F127的自我组装,形成具有溶酶体作用的纳米细胞 (BDPdNP),以增强细胞吸收.
- 通过特定的分子途径 (NLRP3/GSDMD,caspase-3/GSDME) 在体外和体内评估BDPdNP介导的PTT/PDT,诱导 lysosomal损伤,ICD和 pyroptosis.
- 在小鼠三阴性乳腺癌模型中对自我保护性自抑制的评估和对抗瘤疗效和免疫反应的评估.
主要成果:
- 在激光照射后,BDPd NPs有效地向溶酶体,并诱导显著的溶酶体损伤.
- 通过激活NLRP3 / GSDMD和caspase-3 / GSDME通路,治疗协同触发了热和ICD.
- 溶酶体功能障碍有效地阻断了PTT/PDT诱导的自,提高了治疗结果.
- 内和静脉注射BDPdNP显著抑制瘤生长,刺激抗瘤免疫反应,并延长小鼠的生存时间.
结论:
- 开发的BDPdNP代表了癌症免疫疗法的有效策略,通过将PTT/PDT与溶酶体向结合起来.
- 这种方法有效地诱导ICD和热,同时克服自性抵抗,从而产生强大的抗瘤效应.
- 这些发现突出了针对亚细胞器官的光疗在提高癌症治疗疗效方面的潜力.
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