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首页> 外文期刊>Biomaterials Science >Engineering microglia as intraoperative optical imaging agent vehicles potentially for fluorescence-guided surgery in gliomas
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Engineering microglia as intraoperative optical imaging agent vehicles potentially for fluorescence-guided surgery in gliomas

机译：工程微胶质胶质细胞作为术中光学成像代理车辆可能用于荧光肿的荧光导向手术

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摘要

Surgical resection currently remains the mainstay of treatment for patients with gliomas of any grade. The maximum extent of surgical resection is associated with a long-term disease control; however, maximal resection of the brain tumor possibly results in additional neurological deficits. Therefore, improving the precision in brain tumor surgery by visual identification and screening of tumor cells can help to tackle this devastating disease. In the present study, BV2 microglial cells were engineered by iron oxide-nanoparticle stimulation as intraoperative optical imaging agent vehicles and loaded with near-infrared fluorescent dye DiD (DiDBV2-Fe) potentially for fluorescence-guided brain tumor surgery. Activation of BV2 microglial cells by citrate-stabilized iron oxide nanoparticles at a concentration of 62.5 mu g mL(-1) significantly inhibited M2 markers (arginase-1 and CD206), which is able to minimize risks of the immunosuppressive effects caused by the M2-like phenotype of microglial cells. Meanwhile, activated BV2 microglial cells showed up-regulation of arylsulfatase A, apolipoprotein E, transferrin, and ferritin heavy chain-1 gene expression that tends to promote microglia transport across the blood-brain barrier (BBB). Compared to DiDBV2 without iron oxide activation, DiDBV2-Fe indicated strong tumor tropism in response to monocyte chemoattractant protein-1 (CCL2) secreted by U87MG tumor cells. In vivo experiments proved that DiDBV2-Fe efficiently crossed the BBB and more than 90% fluorescence intensity generated by activated microglial cells was detected in the brain when administered through the carotid artery in an orthotopic glioblastoma mouse model. Notably, DiDBV2-Fe produced clear tumor border demarcation on near-infrared imaging and exhibited a superior tumor-to-brain fluorescence ratio to commercial 5-aminolevulinic acid. Accumulated DiDBV2-Fe induced a strong fluorescence signal in brain tumor tissue for a prolonged period (4-24 h), which is beneficial to perform complex and time-consuming brain operations. Overall, our study suggests that this newly engineered microglial cell has promise for enabling more accurate brain tumor imaging for fluorescence-guided resections.
机译：外科切除术目前仍然是任何等级胶质瘤患者的治疗中的主干。手术切除的最大程度与长期疾病控制有关;然而，最大切除脑肿瘤可能导致额外的神经缺陷。因此，通过视觉鉴定提高脑肿瘤手术的精度和肿瘤细胞的筛选可以帮助解决这种破坏性疾病。在本研究中，通过氧化铁 - 纳米颗粒刺激设计BV2微胶质细胞作为术中光学成像剂，并且含有近红外荧光染料（DIDBV2-FE）可能用于荧光导向脑肿瘤手术。通过柠檬酸盐稳定的氧化铁纳米颗粒以62.5μggml（-1）的浓度为显着抑制M2标记物（氨基酶-1和CD206）的BV2微胶质细胞的激活，其能够最小化由M2引起的免疫抑制效应的风险 - 般的小胶质细胞表型。同时，活化的BV2微胶质细胞显示芳基硫酸酶A，载脂蛋白E，转移素和铁蛋白重链-1基因表达的上调，其倾向于促进血脑屏障（BBB）的小凝集血糖输送。与没有氧化铁活化的DIDBV2相比，DIDBV2-FE指示强烈的肿瘤热带，响应于U87MG肿瘤细胞分泌的单核细胞化学毒性蛋白-1（CCL2）。在体内实验中，当通过在原位胶质母细胞瘤小鼠模型中施用时，在大脑中检测到DIDBV2-FE有效地越过BBB和超过90％的荧光强度，在大脑中检测到脑中的激活微胶质细胞。值得注意的是，DIDBV2-FE产生了近红外成像的透明肿瘤边界划分，并向商业5-氨基乙酰丙酸表现出优异的肿瘤对脑荧光比。积累的DIDBV2-FE诱导脑肿瘤组织的强荧光信号长时间（4-24小时），这有利于进行复杂和耗时的脑操作。总体而言，我们的研究表明，这种新工程化的小胶质细胞具有能够为荧光引导切除的更准确的脑肿瘤成像。

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  • 来源
    《Biomaterials Science》 |2020年第4期|共10页
  • 作者

    Guo Ling; Zhang Xiaochen; Wei Runxiu; Li Gaojie; Sun Bingzhi; Zhang Hongbo; Liu Dan; Wang Cuifeng; Feng Min;

  • 作者单位

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Southern Med Univ Zhujiang Hosp Dept Neurosurg Guangzhou 510282 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

    Sun Yat Sen Univ Sch Pharmaceut Sci Guangzhou 510006 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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