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多西紫杉醇肺靶向脂质体在兔 VX2 原位肺癌模型中对肺内肿瘤的增强抗肿瘤作用。

Enhanced antitumor effect on intrapulmonary tumors of docetaxel lung-targeted liposomes in a rabbit model of VX2 orthotopic lung cancer.

机构信息

Pharmacy College, Chongqing Medical University, Chongqing, 400016, China.

Department of Pharmacy, Chongqing Medical and Pharmaceutical college, Chongqing, 401331, China.

出版信息

Sci Rep. 2017 Aug 30;7(1):10069. doi: 10.1038/s41598-017-10530-8.

DOI:10.1038/s41598-017-10530-8
PMID:28855665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5577178/
Abstract

Allergic reactions and severe systemic toxicity are two major challenges for the clinical application of docetaxel (DTX) for treatment of non-small-cell lung cancer (NSCLC). We developed a novel lung-targeted DTX-loaded liposome (DTX-LP), an efficient drug delivery system, with a patented DBaumNC technology to overcome these deficiencies. In the present study, we describe the targeting activity, tumor inhibition rate (TIR), survival, pathology, tumor apoptosis and metabolism of DTX after intravenous injection of DTX-LP compared to the DTX injection (DTX-IN) formulation based on the VX2 orthotopic lung cancer rabbit model. Biodistribution studies revealed the highest accumulation in lung and tumor within 12 h after the injection of DTX-LP. The increased TIR indicates that the growth of tumor was slowed. Pathology tests demonstrated that DTX-LP can reduce metastasis and toxicity to non-targeted organs, leading to greatly extended survival time and improved survival of tumor-bearing rabbits. Flow cytometry and immunohistochemistry confirmed that DTX-LP is highly efficacious in tumor tissue, leading to a significant increase of tumor apoptosis and decrease of proliferation and angiogenesis. The results from this study demonstrate the increased intrapulmonary tumor targeting activity, enhanced antitumor effect and reduced toxicity of DTX-LP compared to DTX-IN and highlight its clinical prospects for NSCLC therapy.

摘要

过敏反应和严重的全身毒性是紫杉烷（DTX）治疗非小细胞肺癌（NSCLC）临床应用的两大挑战。我们开发了一种新型的肺部靶向载多西紫杉醇脂质体（DTX-LP），这是一种高效的药物递送系统，采用专利的 DBaumNC 技术来克服这些缺陷。在本研究中，我们描述了基于 VX2 原位肺癌兔模型，静脉注射 DTX-LP 与 DTX 注射液（DTX-IN）制剂相比的靶向活性、肿瘤抑制率（TIR）、生存、病理学、肿瘤凋亡和代谢情况。生物分布研究显示，在注射 DTX-LP 后 12 小时内，肺和肿瘤中的积累最高。增加的 TIR 表明肿瘤生长速度减慢。病理学测试表明，DTX-LP 可以减少转移和对非靶向器官的毒性，从而大大延长荷瘤兔的存活时间和提高其存活率。流式细胞术和免疫组织化学证实，DTX-LP 在肿瘤组织中具有很高的疗效，导致肿瘤凋亡显著增加，增殖和血管生成减少。与 DTX-IN 相比，这项研究的结果表明 DTX-LP 具有增强的肺内肿瘤靶向活性、增强的抗肿瘤作用和降低的毒性，突出了其在 NSCLC 治疗中的临床前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/27ea58396cea/41598_2017_10530_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/439038d4c89a/41598_2017_10530_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/d8345986b06f/41598_2017_10530_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/5f48788bcaa1/41598_2017_10530_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/c6a3f4570b1c/41598_2017_10530_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/7df4ad33f50f/41598_2017_10530_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/baae026d818f/41598_2017_10530_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/69efeac2d9af/41598_2017_10530_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/adb5da3f874a/41598_2017_10530_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/af226e085b2e/41598_2017_10530_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/27ea58396cea/41598_2017_10530_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/439038d4c89a/41598_2017_10530_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/d8345986b06f/41598_2017_10530_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/5f48788bcaa1/41598_2017_10530_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/c6a3f4570b1c/41598_2017_10530_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/7df4ad33f50f/41598_2017_10530_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/baae026d818f/41598_2017_10530_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/69efeac2d9af/41598_2017_10530_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/adb5da3f874a/41598_2017_10530_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/af226e085b2e/41598_2017_10530_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/144e/5577178/27ea58396cea/41598_2017_10530_Fig10_HTML.jpg

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