A novel cancer targeting approach based on estrone anchored stealth liposome for site-specific breast cancer therapy
Authors: Rishi Paliwal
Shivani Rai Paliwal
S P Vyas
Abhinav Mehta
Neeraj Mishra
Journal: Current Cancer Drug Targets (2010)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: estrogen receptor; anticancer drug delivery; pegylated liposome; breast cancer treatment; estrone
Affiliations: Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Viswavidyalaya, Sagar (M.P.), India.

Abstract:  We here report the successful utilization of estrogen receptor (ER) for the delivery of anticancer drug doxorubicin (DOX) encapsulated within pegylated liposome for the treatment of breast cancer. Estrone (ES) was anchored as ligand on to stealth liposome (ES-SL-DOX) for targeting to ERs. In vitro cytotoxicity study was conducted on ER positive and negative breast carcinoma cells. The fluorescent microscopy studies were performed with estrone anchored stealth liposome (ES-SL) loaded with 6-carboxyfluorescein (6-CF). Pharmacokinetic, tissue distribution studies and tumor growth inhibition were carried out followed by intravenous (i.v.) administration of liposomal formulations. ES-SL-DOX demonstrated strongest cytotoxicity to the ER positive cell lines as compared to non-targeted formulations i.e. SL-DOX and plain DOX confirming that ES-SL-DOX was effectively taken up by cells expressing ERs. The half-life (t(1/2)) of SL-DOX and ES-SL-DOX was about 9 and 13 fold higher than that of the free DOX, respectively. Accumulation of ES-SL-DOX in the tumor tissue was 24.27 and 6.04 times higher as compared to free DOX and SL-DOX respectively, after 8 h. ES-SL-DOX at a dose of 5 mg DOX/kg resulted in effective retardation of tumor growth. These findings support that estrogen receptor(s) may be utilized as potential target for chemotherapy of cancers and estrone anchored stealth liposomes could be one of the promising solutions for the delivery of anticancer agent to breast tumors with reduced side-effects. 

Retracted: No

PubPeer comments:
 Please reveal the authorized source of the luciferase vector used to generate cancer xenograft IVIS data in this paper and the following papers. IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1 2. Chen X, Chen F, Ren Y, Weng G, Xu L, Xue X, Keng PC, Lee SO, Chen Y. J Cancer Res Clin Oncol. 2019 Apr 24. doi: 10.1007 s00432-019-02917-z. [Epub ahead of print] PMID: 31020420 Neuroendocrine differentiation contributes to radioresistance development and metastatic potential increase in non-small cell lung cancer. Zhu R, Yang X, Xue X, Shen M, Chen F, Chen X, Tsai Y, Keng PC, Chen Y, Lee SO, Chen Y. Biochim Biophys Acta Mol Cell Res. 2018 Dec;1865(12):1878-1890. doi: 10.1016 j.bbamcr.2018.09.005. Epub 2018 Sep 15. PMID:30262435 FASN-TGF-u03b21-PD-L1 axis contributes to the development of resistance to NK cell cytotoxicity of cisplatin-resistant lung cancer cells. Shen M, Tsai Y, Zhu R, Keng PC, Chen Y, Chen Y, Lee SO. Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Mar;1863(3):313-322. doi: 10.1016 j.bbalip.2017.12.012. Epub 2018 Jan 3. PMID:29306075 Radiation alters PD-L1 NKG2D ligand levels in lung cancer cells and leads to immune escape from NK cell cytotoxicity via IL-6-MEK Erk signaling pathway. Shen MJ, Xu LJ, Yang L, Tsai Y, Keng PC, Chen Y, Lee SO, Chen Y. Oncotarget. 2017 Jul 12;8(46):80506-80520. doi: 10.18632 oncotarget.19193. eCollection 2017 Oct 6. PMID:29113321 Enhancing NK cell-mediated cytotoxicity to cisplatin-resistant lung cancer cells via MEK Erk signaling inhibition. Yang L, Shen M, Xu LJ, Yang X, Tsai Y, Keng PC, Chen Y, Lee SO. Sci Rep. 2017 Aug 11;7(1):7958. doi: 10.1038 s41598-017-08483-z. PMID:28801607 A FASN-TGF-u03b21-FASN regulatory loop contributes to high EMT metastatic potential of cisplatin-resistant non-small cell lung cancer. Yang L, Zhang F, Wang X, Tsai Y, Chuang KH, Keng PC, Lee SO, Chen Y. Oncotarget. 2016 Aug 23;7(34):55543-55554. doi: 10.18632 oncotarget.10837. , 
 #1 PcDNA3.1-luciferase for all these papers. , 
 #2 How did this laboratory acquire this pcDNA3.1- Luciferase before this year? Please provide the information regarding the source giving this laboratory the permission to use this vector. ,