Targeted Liposomal Chemotherapies to Treat Triple-Negative Breast Cancer.
Yingnan SiYa ZhangHanh Giai NgoJia-Shiung GuanKai ChenQing WangAjeet Pal SinghYuanxin XuLufang ZhouEddy Shih-Hsin YangXiaoguang Margaret LiuPublished in: Cancers (2021)
Triple-negative breast cancers (TNBCs) are highly aggressive and recurrent. Standard cytotoxic chemotherapies are currently the main treatment options, but their clinical efficacies are limited and patients usually suffer from severe side effects. The goal of this study was to develop and evaluate targeted liposomes-delivered combined chemotherapies to treat TNBCs. Specifically, the IC50 values of the microtubule polymerization inhibitor mertansine (DM1), mitotic spindle assembly defecting taxane (paclitaxel, PTX), DNA synthesis inhibitor gemcitabine (GC), and DNA damage inducer doxorubicin (AC) were tested in both TNBC MDA-MB-231 and MDA-MB-468 cells. Then we constructed the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) tagged liposomes and confirmed its TNBC cell surface binding using flow cytometry, internalization with confocal laser scanning microscopy, and TNBC xenograft targeting in NSG female mice using In Vivo Imaging System. The safe dosage of anti-EGFR liposomal chemotherapies, i.e., <20% body weight change, was identified. Finally, the in vivo anti-tumor efficacy studies in TNBC cell line-derived xenograft and patient-derived xenograft models revealed that the targeted delivery of chemotherapies (mertansine and gemcitabine) can effectively inhibit tumor growth. This study demonstrated that the targeted liposomes enable the new formulations of combined therapies that improve anti-TNBC efficacy.
Keyphrases
- epidermal growth factor receptor
- cancer therapy
- drug delivery
- monoclonal antibody
- tyrosine kinase
- dna damage
- body weight
- small cell lung cancer
- high resolution
- flow cytometry
- cell cycle arrest
- advanced non small cell lung cancer
- cell surface
- end stage renal disease
- drug release
- ejection fraction
- single molecule
- oxidative stress
- squamous cell carcinoma
- optical coherence tomography
- breast cancer cells
- type diabetes
- peritoneal dialysis
- wastewater treatment
- metabolic syndrome
- early onset
- weight loss
- patient reported outcomes
- cell proliferation
- insulin resistance
- locally advanced
- single cell
- simultaneous determination
- young adults
- rectal cancer