放射治疗,尽管它的精确性和非侵入性,通常由于癌症干细胞(CSC)的耐药性而失败,其特点是高度的自我更新能力和优越的DNA修复机制。这些细胞可以逃避RT并导致肿瘤复发和转移。为了应对这一挑战,介绍了一种名为PB的新型输送系统。该系统将脂质体与血小板膜结合起来,以包封双-2-(5-苯基乙酰氨基-1,2,4-噻二唑-2-基)乙基硫醚(BPTES),从而增强其在肿瘤部位的递送和释放。此外,该系统不仅有效地靶向CSC,而且在X射线照射下增加BPTES的局部浓度,降低肿瘤细胞中谷胱甘肽的水平,从而增加氧化应激和损伤线粒体。PB引起的线粒体损伤作为STING信号的起始点,其介导cGAS-STING途径相关蛋白表达的显著上调,从而放大STING信号。全身静脉给予PB显著促进DC成熟和CD8+T细胞浸润,从而引发强烈的抗肿瘤作用。总的来说,该PB系统提供了克服CSC相关耐药性的有效方法,并为未来的癌症治疗方案提供了有希望的方法.
Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols.