Targeting lung cancer stem cells using combination of Tel and Docetaxel liposomes in 3D cultures and tumor xenografts

被引:21
作者
Arthur, Peggy [1 ]
Patel, Nilkumar [1 ]
Surapaneni, Sunil Kumar [1 ]
Mondal, Arindam [2 ]
Gebeyehu, Aragaw [1 ]
Bagde, Arvind [1 ]
Kutlehria, Shallu [1 ]
Nottingham, Ebony [1 ]
Singh, Mandip [1 ]
机构
[1] Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA
[2] Rutgers State Univ, New Brunswick, NJ USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Cancer Stem Cells (CSC); Docetaxel Loaded PEGylated Liposomes (DTXPL); Docetaxel (DTX); Telmisartan (Tel); Non-small Cell Lung Cancer (NSCLC); Resistance; ACTIVATED RECEPTOR-GAMMA; GROWTH-FACTOR-BETA; DRUG-DELIVERY; PEGYLATED LIPOSOMES; SOLID TUMORS; CD44; TELMISARTAN; RESISTANCE; CARCINOMA; NANOPARTICLES;
D O I
10.1016/j.taap.2020.115112
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cancer stem cells (CSCs) accounts for recurrence and resistance to chemotherapy in various tumors. Efficacy of chemotherapeutic drugs is limited by tumor stromal barriers, which hinder their penetration into deep tumor sites. We have earlier shown telmisartan (Tel) pretreatment prior to Docetaxel (DTX) administration enhances anti-cancer effects in non-small cell lung cancer (NSCLC). Herein, we demonstrated for the first time the efficacy of Docetaxel liposomes (DTXPL) in combination with Tel in 3D cultures of H460 cells by using polysaccharide-based hydrogels (TheWell Biosciences) and also in xenograft model of DTX resistant H460 derived CD133(+) lung tumors. DTXPL and Tel combination showed enhanced cytotoxicity in H460 WT 3D cultures by two folds. In H460 3D cultures, Tel pretreatment showed increased liposomal uptake. DTXPL and Tel combination treated tumors showed reduction in tumor volume (p < .001), increased apoptosis and downregulation of CSC markers (p < .01) in H460 WT and DTX resistant CD133(+) xenograft models.
引用
收藏
页数:11
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