通过支柱[5]基于arene的宿主-客人识别对瘤微环境进行超分子调节
Yunxuan Feng1, Shaolong Qi1, Xinyang Yu1
1Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, P. R. China.
Journal of the American Chemical Society
|August 3, 2023
概括
这项研究介绍了一种新的纳米药物TAPP,该药物可以重编程瘤微环境 (TME). 通过减少免疫抑制和增强抗瘤免疫反应以长期抑制瘤,TAPP可以增强免疫治疗.
科学领域:
- 生物医学工程
- 纳米医学
- 癌症免疫疗法
背景情况:
- 固体瘤的免疫疗法耐药性是一个重大挑战,通常与低氧瘤微环境 (TME) 相关,该微环境促进免疫规避.
- 在TME中的低氧诱导因子1-α (HIF-1α) 和多氨酸有助于瘤细胞存活和免疫抑制.
- 重新编程TME为提高癌症免疫疗法的有效性提供了一个有前途的策略.
研究的目的:
- 开发一种能够重塑免疫抑制TME的超分子纳米药物 (TAPP).
- 在TAPP中结合化疗和化学动力学治疗 (CDT),以获得协同作用的抗瘤疗法.
- 研究TAPP增强免疫检查点阻塞 (ICB) 疗法的潜力.
主要方法:
- 使用宿主-客分子识别和金属协调设计的超分子纳米医学 (TAPP).
- 在TAPP中封装Tamoxifen (Tmx) 和Fe3+用于联合治疗作用.
- 对TAPP降低HIF-1α调节,消除瘤多氨基和诱导免疫细胞死亡的能力的评估.
主要成果:
- 通过降低HIF-1α和消除多氨酸,TAPP有效地重新编程了免疫抑制TME.
- 在TAPP中,Tmx和Fe3+的组合诱导了增强的免疫细胞死亡.
- TAPP与免疫检查点阻塞 (ICB) 疗法协同作用,促进细胞毒性T淋巴细胞透和长期瘤抑制.
结论:
- 超分子纳米药TAPP显示出重塑TME并克服免疫疗法抵抗性的显著潜力.
- 基于TAPP的联合治疗,包括化疗,CDT和ICB,为增强抗瘤免疫提供了有效的策略.
- 这种重新编程方式有望实现持续的瘤抑制和改善患者在固体瘤中的结果.
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