Novel pH-sensitive nanoformulated docetaxel as a potential therapeutic strategy for the treatment of cholangiocarcinoma

Journal of Nanobiotechnology

Research

Lei Wang¹  Hui Zhao²  Nan Du²  Xiao-Song Li²  Ling Wan²  Hong-Ying Ma²  Lin-Ping Song² 

[1] Department of Medical, The First Affiliated Hospital of the General Hospital of the PLA, No. 51 Fucheng Road, Haidian District, 100048, Beijing, China;The Second Department of Oncology, The First Affiliated Hospital of the General Hospital of the PLA, 100048, Beijing, China;

关键词: Cholangiocarcinoma;    Polymeric micelles;    Docetaxel;    Apoptosis;    Cancer chemotherapy;   

DOI  :  10.1186/s12951-015-0066-8

 received in 2014-11-19, accepted in 2015-01-07,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCholangiocarcinoma (CC) is one of the fatal malignant neoplasms with poor prognosis. The traditional chemotherapy has been resistant to CC and does not improve the quality of life. The aim of the present study is to investigate the potential of chondroitin sulphate (CS)-histamine (HS) block copolymer micelles to improve the chemotherapeutic efficacy of docetaxel (DTX).ResultspH-responsive property of CS-HS micelles was utilized to achieve maximum therapeutic efficacy in CC. In the present study, docetaxel-loaded CS-HS micelles (CSH-DTX) controlled the release of drug in the basic pH while rapidly released its cargo in the tumor pH (pH 5 and 6.8) possibly due to the breakdown of polymeric micelles. A nanosize of <150 nm will allow its accumulation in the tumor interstitial spaces via EPR effect. CSH-DTX effectively killed the cancer kills in a time- and concentration-dependent manner and showed pronounced therapeutic action than that of free drug at all-time points. CSH-DTX resulted in higher apoptosis of cancer cells with ~30% and ~50 of cells in early apoptosis quadrant when treated with 100 and 1000 ng/ml of equivalent drug. The micellar formulations showed remarkable effect in controlling the tumor growth and reduced the overall tumor volume to 1/5th to that of control and half to that of free drug treated group with no sign of drug-related adverse effects. Immunohistochemical analysis of tumor sections showed that fewer number of Ki-67 cells were present in CSH-DTX treated group comparing to that of free DTX treated group.ConclusionOur data suggests that nanoformulation of DTX could potentially improve the chemotherapy treatment in cholangiocarcinoma as well as in other malignancies.

【 授权许可】

Unknown   
© Du et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.