TP53 缺失通过上调 NF-κB-IFN-β-MHC-Ia 信号促进骨肉瘤对 NK 细胞的抵抗
TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.
TP53失活是骨肉瘤(OS)发生中的关键事件,也是其侵袭性的基础,但其在肿瘤-免疫相互作用中的作用仍知之甚少。
英文原题:MPI-Guided Photothermal Therapy of Prostate Cancer Using Stem Cell Delivery of Magnetotheranostic Nanoflowers.
肿瘤光热治疗(PTT)的疗效关键取决于纳米颗粒(NP)在肿瘤内的广泛分布与滞留。
癌症光热疗法(PTT)的疗效在很大程度上取决于纳米颗粒(NP)能否广泛分布并滞留于肿瘤内。然而,瘤内注射裸NP可能造成分散不佳和反流,继而发生泄漏并被迅速清除,限制疗效并增加脱靶毒性。为克服这些局限,我们采用具有肿瘤趋向性的人间充质干细胞(hMSC)作为磁诊疗金-氧化铁纳米花(GIONF)的递送载体。与注射裸GIONF相比,该方法实现了更广泛的瘤内分布和更持久的滞留。近红外激光照射下,GIONF-hMSC显示出更强的加热性能,同时具有明显的磁粒子成像(MPI)信号,可无创定量追踪其全身生物分布。在GIONF-hMSC滞留达到峰值时进行激光照射,可完全消融肿瘤,且治疗后90天内未见复发。这些结果首次展示了利用MPI评估瘤内注射的细胞内纳米颗粒与裸纳米颗粒的滞留和泄漏,为采用细胞磁诊疗推进PTT提供依据。
The efficacy of photothermal therapy (PTT) of cancer critically depends on widespread nanoparticle (NP) distribution and retention within the tumor. However, intratumoral (i.t.) injection of naked NPs may result in poor dispersion and backflow resulting in leakage and rapid clearance, limiting therapeutic outcome and increasing off-target toxicity. To overcome these limitations, we employed tumor-tropic human mesenchymal stem cells (hMSCs) as delivery vehicles for magnetotheranostic gold-iron oxide nanoflowers (GIONF), enabling widespread i.t. distribution and sustained retention in contrast to injection of naked GIONF. GIONF-hMSCs demonstrated superior heating performance under near-infrared laser irradiation while exhibiting a strong magnetic particle imaging (MPI) signal, allowing for noninvasive quantitative tracking of their whole body biodistribution. Laser irradiation at peak GIONF-hMSC retention resulted in complete tumor ablation without recurrence up to 90 days post-treatment. These results are a first demonstration of using MPI to evaluate the retention and leakage of i.t.-injected intracellular versus naked nanoparticles for advancing PTT with cellular magnetotheranostics.
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