Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid.
Qin WangYinan ZhongWenting LiuZemin WangLiqin GuXuejiao LiJiqing ZhengHuan DuZhiyuan ZhongFang XiePublished in: Drug delivery (2019)
Despite the development of treatment options in breast cancer, many patients die of recurrence and metastasis. Owing to enhanced permeability and retention in solid tumor tissue, nanoparticle (NP) delivery systems have been emerged as novel strategy in cancer chemotherapy. As extracellular matrix, glycosaminoglycan hyaluronan (HA) could bind its surface receptor adhesion molecule CD44 which is strongly expressed on breast cancer. We have previously reported a doxorubicin (DOX)-loaded HA-Lys-LA X-NPs (X-NP-DOX) NP delivery system for breast cancer treatment. In this study, we further investigated the antitumor effect of X-NP-DOX NP delivery system using low-dose DOX in both in vitro and in vivo systems. We demonstrated that low-dose X-NP-DOX possessed the ability for inhibiting MCF-7 breast cancer cell growth, invasion, and migration, and inducing apoptosis in vitro. In in vivo experiments, injection of low-dose X-NP-DOX into tumor-bearing mouse resulted in significant reduction of tumor size. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining further revealed that low-dose X-NP-DOX induced higher percentage of apoptotic cells compared with free DOX or saline. Furthermore, our study demonstrated that low-dose X-NP-DOX inhibited Notch1 and Ras/MAPK pathways, decreased cancer stem cell population, and reduced tumorigenesis compared to free DOX in both in vitro and in vivo settings. Owing to its enhanced efficacy and higher targetability compared to free DOX, low-dose DOX delivered by NP system may be a promising novel strategy for breast cancer treatment.
Keyphrases
- low dose
- high dose
- hyaluronic acid
- extracellular matrix
- drug delivery
- cell death
- squamous cell carcinoma
- end stage renal disease
- cancer therapy
- chronic kidney disease
- cell proliferation
- cell cycle arrest
- induced apoptosis
- newly diagnosed
- radiation therapy
- prognostic factors
- cystic fibrosis
- single cell
- high resolution
- cell migration
- atomic force microscopy
- young adults
- diabetic rats
- locally advanced
- breast cancer cells
- candida albicans
- patient reported outcomes