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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo.
Nanoparticles and Mesenchymal Stem Cell (MSC) Therapy for Cancer Treatment: Focus on Nanocarriers and a si-RNA CXCR4 Chemokine Blocker as Strategies for Tumor Eradication In Vitro and In Vivo.
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间充质干细胞(MSC)对肿瘤缺氧微环境具有很强的趋向性。将纳米颗粒与MSC结合,可在体外及癌症啮齿动物体内模型中抑制肿瘤生长。将纳米颗粒与MSC表面共价偶联,可显著增加肿瘤部位的药物递送量。基于金、二氧化硅和硅酸盐、金刚石、银及铜等材料的纳米抗血管生成系统可在体外阻止肿瘤生长。例如,乙醇酸多聚偶联物可增强纳米颗粒药物递送,已有研究在人体MSC中报告了这一方法。利用荧光颗粒(香豆素-6染料)标记可通过组织荧光发射识别肿瘤细胞;不同类型的纳米颗粒与MSC偶联后,可通过无创成像追踪迁移并在肿瘤内检测,从而证明此方法可行且成功。
然而,若要临床应用,仍需改善生物安全性、疗效、纳米颗粒长期稳定性及药物释放能力。MSC既是纳米颗粒药物递送载体,自身毒性也较低,但网状内皮器官清除作用会导致其在肿瘤部位积聚效率不高。为解决这些问题,应改进MSC对载药纳米颗粒的内化或偶联。
最后,CXCR4可能是免疫治疗和癌症治疗的有前景靶点,因为递送siRNA敲低这种α趋化因子受体或拮抗CXCR4,已被证明可破坏肿瘤-基质相互作用。
Mesenchymal stem cells (MSCs) have a high tropism for the hypoxic microenvironment of tumors. The combination of nanoparticles in MSCs decreases tumor growth in vitro as well as in rodent models of cancers in vivo. Covalent conjugation of nanoparticles with the surface of MSCs can significantly increase the drug load delivery in tumor sites. Nanoparticle-based anti-angiogenic systems (gold, silica and silicates, diamond, silver, and copper) prevented tumor growth in vitro.
For example, glycolic acid polyconjugates enhance nanoparticle drug delivery and have been reported in human MSCs. Labeling with fluorescent particles (coumarin-6 dye) identified tumor cells using fluorescence emission in tissues; the conjugation of different types of nanoparticles in MSCs ensured success and feasibility by tracking the migration and its intratumor detection using non-invasive imaging techniques.
However, the biosafety and efficacy; long-term stability of nanoparticles, and the capacity for drug release must be improved for clinical implementation. In fact, MSCs are vehicles for drug delivery with nanoparticles and also show low toxicity but inefficient accumulation in tumor sites by clearance of reticuloendothelial organs. To solve these problems, the internalization or conjugation of drug-loaded nanoparticles should be improved in MSCs.
Finally, CXCR4 may prove to be a promising target for immunotherapy and cancer treatment since the delivery of siRNA to knock down this alpha chemokine receptor or CXCR4 antagonism has been shown to disrupt tumor-stromal interactions.
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