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通过化学基因共递纳米颗粒进行代谢重编程,用于头部和部状细胞癌的化学免疫疗法

Wenqing Zou¹, Bingyue Huo¹, Yaqin Tu¹

¹Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Acta biomaterialia

|April 19, 2025

概括

这项研究开发了新的纳米粒子,将金药物与基因编辑结合起来,以准头癌. 这种化疗免疫治疗方法通过重编程瘤微环境,有效地减少了瘤和毒性.

科学领域:

生物医学工程生物医学工程
癌症治疗癌症治疗
纳米技术纳米技术

背景情况:

基于的药物对于癌症治疗至关重要,但面临着瘤代谢免疫微环境失调的挑战.
在瘤中异常的乳酸积累有助于免疫抑制和治疗效率降低.
向瘤代谢和免疫微环境对于提高癌症治疗结果至关重要.

研究的目的:

设计多功能纳米粒子 (PPPtIV NP) 以同时提供西斯原药 (PtIV) 和CRISPR/Cas9-PKM2等离子体.
研究这些纳米颗粒在头部和部状细胞癌 (HNSCC) 的协同化疗-免疫治疗效应.
评估逆转乳酸介导免疫抑制和增强抗瘤免疫力的潜力.

主要方法:

PPPtIVNP的制造是通过聚乙氨基的静电自组装来制造的.
在纳米颗粒中同时封装PtIV前药物和CRISPR/Cas9-PKM2等离子体.
在体外和体内对纳米粒子介导药物输送,基因编辑,代谢重编程和免疫反应调节的评估.
在HNSCC模型中评估治疗疗效和毒性.

主要成果:

PPPtIV NPs成功地将PtIV前和CRISPR/Cas9-PKM2等离子体输送到癌细胞中.
通过CRISPR/Cas9抑制PKM2,抑制了Warburg效应,减少了乳酸生产,并降低了HIF-1α和PD-L1.
这些纳米粒子诱导了DNA损伤,亡,并重塑了免疫微环境,增强了T细胞介导的免疫力.
与西斯普拉丁相比,PPPtIV NP显示出优越的抗瘤疗效,对抗初级和复发性瘤,毒性降低.

结论:

设计的PPPTIV纳米平台为HNSCC治疗提供了一种协同化学免疫治疗策略.
同时增强DNA损伤和通过代谢重编程逆转免疫抑制是一种有希望的方法.
这种纳米技术驱动的战略为结合基药物与免疫代谢干预提供了宝贵的见解.

关键词:

化学基因纳米颗粒是什么化疗-免疫疗法是一种化学免疫疗法.西斯普拉丁前药物 (Pt(IV))乳酸盐是一种乳酸盐.代谢 - 免疫重编程

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