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A Light‐Triggered Mesenchymal Stem Cell Delivery System for Photoacoustic Imaging and Chemo‐Photothermal Therapy of Triple Negative Breast Cancer

机译:一种轻触发的间充质干细胞递送系统用于三重阴性乳腺癌的光声成像和化学光热疗法。

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摘要

Targeted therapy is highly challenging and urgently needed for patients diagnosed with triple negative breast cancer (TNBC). Here, a synergistic treatment platform with plasmonic–magnetic hybrid nanoparticle (lipids, doxorubicin (DOX), gold nanorods, iron oxide nanocluster (LDGI))–loaded mesenchymal stem cells (MSCs) for photoacoustic imaging, targeted photothermal therapy, and chemotherapy for TNBC is developed. LDGI can be efficiently taken up into the stem cells with good biocompatibility to maintain the cellular functions. In addition, CXCR4 on the MSCs is upregulated by iron oxide nanoparticles in the LDGI. Importantly, the drug release and photothermal therapy can be simultaneously achieved upon light irradiation. The released drug can enter the cell nucleus and promote cell apoptosis. Interestingly, light irradiation can control the secretion of cellular microvehicles carrying LDGI for targeted treatment. A remarkable in vitro anticancer effect is observed in MDA‐MB‐231 with near‐infrared laser irradiation. In vivo studies show that the MSCs‐LDGI has the enhanced migration and penetration abilities in the tumor area via both intratumoral and intravenous injection approaches compared with LDGI. Subsequently, MSCs‐LDGI shows the best antitumor efficacy via chemo‐photothermal therapy compared to other treatment groups in the TNBC model of nude mice. Thus, MSCs‐LDGI multifunctional system represents greatly synergistic potential for cancer treatment.
机译:对于诊断为三阴性乳腺癌(TNBC)的患者,靶向治疗具有很高的挑战性和迫切需要。在这里,使用等离子-磁性混合纳米颗粒(脂质,阿霉素(DOX),金纳米棒,氧化铁纳米簇(LDGI))-负载的间充质干细胞(MSC)进行光声成像,靶向光热疗法和TNBC化疗的协同治疗平台被开发。 LDGI可以有效地吸收到具有良好生物相容性的干细胞中,以维持细胞功能。此外,LDGI中的氧化铁纳米颗粒会上调MSCs上的CXCR4。重要的是,在光照射下可以同时实现药物释放和光热疗法。释放的药物可以进入细胞核并促进细胞凋亡。有趣的是,光照射可以控制带有LDGI的细胞微载体的分泌,以进行靶向治疗。在近红外激光照射下的MDA-MB-231中观察到了显着的体外抗癌作用。体内研究表明,与LDGI相比,通过肿瘤内和静脉内注射方法,MSCs-LDGI在肿瘤区域具有增强的迁移和穿透能力。随后,与TNBC裸鼠模型中的其他治疗组相比,MSCs-LDGI通过化学光热疗法显示出最佳的抗肿瘤功效。因此,MSCs-LDGI多功能系统代表了巨大的协同治疗癌症的潜力。

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