基于脂质纳米胶囊的安全凝胶技术用于靶向淋巴结并对抗SCID-CB17小鼠原位非小细胞肺癌模型的纵隔转移。

Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice.

作者信息

Wauthoz Nathalie, Bastiat Guillaume, Moysan Elodie, Cieślak Anna, Kondo Kazuya, Zandecki Marc, Moal Valérie, Rousselet Marie-Christine, Hureaux José, Benoit Jean-Pierre

机构信息

LUNAM Université - Micro et Nanomédecines Biomimétiques, Angers, France; INSERM - U1066 IBS-CHU, Angers, France.

Department of Oncological Medical Services, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.

出版信息

Nanomedicine. 2015 Jul;11(5):1237-45. doi: 10.1016/j.nano.2015.02.010. Epub 2015 Mar 16.

Abstract

UNLABELLED

The purpose of this study is the assessment of gel technology based on a lauroyl derivative of gemcitabine encapsulated in lipid nanocapsules delivered subcutaneously or intravenously after dilution to (i) target lymph nodes, (ii) induce less systemic toxicity and (iii) combat mediastinal metastases from an orthotopic model of human, squamous, non-small-cell lung cancer Ma44-3 cells implanted in severe combined immunodeficiency mice. The gel technology mainly targeted lymph nodes as revealed by the biodistribution study. Moreover, the gel technology induced no significant myelosuppression (platelet count) in comparison with the control saline group, unlike the conventional intravenous gemcitabine hydrochloride treated group (P<0.05). Besides, the gel technology, delivered subcutaneously twice a week, was able to combat locally mediastinal metastases from the orthotopic lung tumor and to significantly delay death (P<0.05) as was the diluted gel technology delivered intravenously three times a week.

FROM THE CLINICAL EDITOR

Lung cancer is one of the leading causes of mortality worldwide. A significant proportion of patients with this disease have lymph node metastasis. In this study, the authors investigated the use of lipid nanocapsules, loaded with the lipophilic pro-drug gemcitabine for targeting tumors in lymph nodes after subcutaneous injection. This delivery method was shown to be effective in controlling tumor progression and may be useful in future clinical use.

摘要

未标记

本研究的目的是评估基于吉西他滨月桂酰衍生物的凝胶技术,该衍生物封装在脂质纳米胶囊中,在稀释后通过皮下或静脉注射给药,以(i)靶向淋巴结,(ii)降低全身毒性,以及(iii)对抗严重联合免疫缺陷小鼠体内植入的人鳞状非小细胞肺癌Ma44 - 3细胞原位模型的纵隔转移。生物分布研究表明,凝胶技术主要靶向淋巴结。此外,与对照盐水组相比,凝胶技术未诱导明显的骨髓抑制(血小板计数),这与传统静脉注射盐酸吉西他滨治疗组不同(P<0.05)。此外,每周皮下给药两次的凝胶技术能够对抗原位肺肿瘤的局部纵隔转移,并显著延迟死亡(P<0.05),每周静脉注射三次的稀释凝胶技术也是如此。

来自临床编辑

肺癌是全球主要的死亡原因之一。该疾病的很大一部分患者有淋巴结转移。在本研究中,作者研究了负载亲脂性前药吉西他滨的脂质纳米胶囊在皮下注射后靶向淋巴结肿瘤的用途。这种给药方法被证明在控制肿瘤进展方面有效,可能在未来临床应用中有用。

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