A self‐assembled nanomedicine for glucose supply interruption‐amplified low‐temperature photothermal therapy and anti‐prometastatic inflammatory processes of triple‐negative breast cancer

Aggregate Pub Date : 2024-06-25 DOI:10.1002/agt2.622
Mingcheng Wang, Huixi Yi, Zhixiong Zhan, Zitong Feng, Gang‐Gang Yang, Yue Zheng, Dong‐Yang Zhang
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Abstract

The poor prognosis of triple‐negative breast cancer (TNBC) results from its high metastasis, whereas inflammation accompanied by excessive reactive oxygen species (ROS) is prone to aggravate tumor metastasis. Although photothermal therapy (PTT) has extremely high therapeutic efficiency, the crafty tumor cells allow an increase in the expression of heat shock proteins (HSPs) to limit its effect, and PTT‐induced inflammation is also thought to be a potential trigger for tumor metastasis. Herein, myricetin, iron ions, and polyvinylpyrrolidone were utilized to develop nanomedicines by self‐assembly strategy for the treatment of metastatic TNBC. The nanomedicines with marvelous water solubility and dispersion can inhibit glucose transporter 1 and interfere with mitochondrial function to block the energy supply of tumor cells, achieving starvation therapy on TNBC cells. Nanomedicines with excellent photothermal conversion properties allow down‐regulating the expression of HSPs to enhance the effect of PTT. Interestingly, the broad spectrum of ROS scavenging ability of nanomedicines successfully attenuates PTT‐induced inflammation as well as influences hypoxia‐inducible factors‐1α/3‐phosphoinositide‐dependent protein kinase 1 related pathway through glycometabolism inhibition to reduce tumor cell metastasis. Moreover, the nanomedicines have negligible side effects and good clinical application prospects, which provides a valuable paradigm for the treatment of metastatic TNBC through glycometabolism interference, anti‐inflammation, starvation, and photothermal synergistic therapy.
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一种自组装纳米药物,用于葡萄糖供应中断--增强的低温光热疗法和三阴性乳腺癌的抗转移炎症过程
三阴性乳腺癌(TNBC)预后不良的原因是其转移率较高,而炎症伴随着过多的活性氧(ROS)容易加重肿瘤的转移。虽然光热疗法(PTT)具有极高的治疗效率,但狡猾的肿瘤细胞会使热休克蛋白(HSPs)的表达增加,从而限制了光热疗法的效果,而PTT诱发的炎症也被认为是肿瘤转移的潜在诱因。本文利用三尖杉酯素、铁离子和聚乙烯吡咯烷酮,通过自组装策略开发出治疗转移性 TNBC 的纳米药物。纳米药物具有良好的水溶性和分散性,能抑制葡萄糖转运体1,干扰线粒体功能,阻断肿瘤细胞的能量供应,实现对TNBC细胞的饥饿治疗。具有优异光热转换特性的纳米药物可以下调 HSPs 的表达,从而增强 PTT 的效果。有趣的是,纳米药物的广谱 ROS 清除能力成功地减轻了 PTT 诱导的炎症反应,并通过抑制糖代谢影响了缺氧诱导因子-1α/3-磷酸肌酸依赖性蛋白激酶 1 的相关通路,从而减少了肿瘤细胞的转移。此外,该纳米药物的副作用微乎其微,具有良好的临床应用前景,为通过糖代谢干扰、抗炎、饥饿和光热协同治疗转移性 TNBC 提供了一种有价值的范式。
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