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Combined delivery and magnetic resonance imaging of neural cell adhesion molecule-targeted doxorubicin-containing liposomes in experimentally induced Kaposi's sarcoma.
在实验诱导的卡波西肉瘤中神经细胞粘附分子靶向含阿霉素脂质体的联合递送和磁共振成像。

摘要

Specific targeting of tumors by combined delivery of drugs and of imaging agents represents an attractive strategy for treatment of cancer. The aim of the present study was to investigate whether neural cell adhesion molecule (NCAM)-targeted liposomes may enhance drug delivery and allow magnetic resonance imaging (MRI) in a severe combined immunodeficient mouse model of NCAM-positive Kaposi's sarcoma. NCAM-binding peptide-coated liposomes loaded with both doxorubicin and a lipophilic gadolinium (Gd) derivative were generated. NCAM-targeted liposomes induced an enhanced in vitro doxorubicin internalization within Kaposi's cells as detected by MRI with respect to untargeted polyethylene glycol liposomes. Internalization resulted in enhanced apoptosis. In vivo weekly administration of NCAM-targeted liposomes containing 5 mg/kg doxorubicin for 4 consecutive weeks induced a significant reduction of tumor mass and vascularization and enhanced cell necrosis and apoptosis with respect to untargeted liposomes. These effects were associated with an enhanced concentration of doxorubicin within the tumor and a reduced systemic toxicity of doxorubicin. By electron microscopy, NCAM-targeted liposomes were detected mainly within tumor cells whereas the untargeted liposomes were mainly accumulated in the extracellular space. Gd-labeled liposomes allowed the MRI visualization of drug delivery in the tumor region. The intensity of MRI signal was partially hampered by the "quenching" of the attainable relaxation enhancement on endosomal entrapment of the Gd-labeled liposomes. In conclusion, targeting NCAM may be a suitable strategy for specific drug delivery and imaging by liposomes in NCAM-expressing tumors. Moreover, treatment with NCAM-targeted liposomes showed enhanced therapeutic effect and reduced toxicity with respect to untargeted liposomes.

译文

通过联合输送药物和显像剂对肿瘤进行特异性靶向治疗是治疗癌症的一种有吸引力的策略。本研究的目的是研究神经细胞粘附分子 (NCAM) 靶向脂质体是否可以增强药物输送并允许磁共振成像 (MRI) 在 NCAM 阳性 Kaposi 肉瘤的严重联合免疫缺陷小鼠模型中。生成了同时装载阿霉素和亲脂性钆 (Gd) 衍生物的 NCAM 结合肽包被脂质体。NCAM-靶向脂质体诱导增强体外多柔比星在 Kaposi 细胞内的内化,通过 MRI 相对于非靶向聚乙二醇脂质体检测到。内化导致细胞凋亡增强。与未靶向脂质体相比,体内每周服用含有 5 mg/kg 阿霉素的 NCAM 靶向脂质体连续 4 周,可显著减少肿瘤质量和血管化,并增强细胞坏死和凋亡。这些效果与肿瘤内阿霉素浓度的增加和阿霉素全身毒性的降低有关。通过电子显微镜检查,NCAM 靶向脂质体主要在肿瘤细胞内被检测到,而非靶向脂质体主要在细胞外空间积累。Gd 标记的脂质体允许在肿瘤区域的药物输送的 MRI 可视化。MRI 信号的强度部分受到 Gd 标记的脂质体内体卡压可达到的松弛增强的 “猝灭”。总之,靶向 NCAM 可能是在 NCAM 表达的肿瘤中通过脂质体进行特异性药物递送和成像的合适策略。此外,与非靶向脂质体相比,NCAM 靶向脂质体治疗显示出增强的治疗效果和降低的毒性。

Neural Cell Adhesion Molecule

神经 免疫球蛋白 临床研究术语
概述  :  

神经细胞粘附分子属于细胞粘附分子免疫球蛋白超家族,在大多数脊椎和无脊椎动物的中枢和外周神经系统中都有表达,是一类在细胞和细胞外基质间起粘附作用的膜表面糖蛋白,为非钙依赖性粘附分子。与学习记忆的关系学习和记忆是两个不相同但却相互依存的大脑的高级功能活动。生理学上认为,学习是大脑在已有信息的基础上,通过行为改变去适应新环境的新的神经活动过程;记忆则是将学习到的知识和信息进行“回放”和保留的神经活动过程。NCAM的表达水平与学习记忆能力有着密切的关系,在学习和记忆的进行中起着重要的作用。将小鼠的N

neural   英 [ˈnjʊərəl]  美 [ˈnʊrəl] 

释    义   adj. 神经的;神经系统的;背的;神经中枢的

例    句   “We could look at what the neural encoding is for this, ” says Mitchell. “这时我们就可以看看神经是如何对此进行编码的了”,米切尔说。

 

cell   英 [sel]  美 [sel] 

释    义   n. 细胞;电池;蜂房的巢室;单人小室

vi. 住在牢房或小室中

同根词   cellularity n. 细胞性;多孔性;细胞结构

例    句   Each cell can only be owned by one feature. 每个细胞才能被拥有一特征。

 

adhesion   英 [ədˈhiːʒn]  美 [ədˈhiːʒn] 

释    义   n. 粘附;支持;固守

同根词   adhesive adj. 粘着的;带粘性的

例句  A low inherent friction and adhesion value also reduces wear. 固有的低摩擦和粘附的价值也减少磨损。

 

molecule   英 [ˈmɒlɪkjuːl]  美 [ˈmɑːlɪkjuːl] 

释    义   n. [化学] 分子;微小颗粒,微粒

例    句   We do all of this to understand the chemistry of one molecule. 我们做了所有这样的事,以了解一个分子的化学性质。

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