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

被引:9
作者
Wang, LiJuan [1 ,2 ]
Li, Rui [1 ]
Che, KeKe [3 ]
Liu, ZhongHong [1 ]
Xiang, ShiFeng [4 ]
Li, MengYa [1 ]
Yu, Yu [1 ]
机构
[1] Chongqing Med Univ, Pharm Coll, Chongqing 400016, Peoples R China
[2] Chongqing Med & Pharmaceut Coll, Dept Pharm, Chongqing 401331, Peoples R China
[3] Chongqing Gen Hosp, Dept Pharm, Chongqing 400014, Peoples R China
[4] Chongqing Gen Hosp, Radiol Dept, Chongqing 400014, Peoples R China
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
基金
中国国家自然科学基金;
关键词
DRUG-DELIVERY; IN-VITRO; RECEPTOR; PHARMACOKINETICS; NANOPARTICLES; STATISTICS; PACLITAXEL; EFFICACY; CELLS;
D O I
10.1038/s41598-017-10530-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:14
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