Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid

Drug Delivery

Yinan Zhong¹  Zhiyuan Zhong¹  Huan Du²  Fang Xie²  Xuejiao Li²  Jiqing Zheng²  Qin Wang³  Wenting Liu⁴  Liqin Gu⁵  Zemin Wang⁶ 

[1] Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou P. R. China;Department of Pathology, Institutes of Biology and Medical Sciences, Soochow University Medical College, Soochow University, Suzhou P. R. China;Department of Pathology, Institutes of Biology and Medical Sciences, Soochow University Medical College, Soochow University, Suzhou P. R. China;Department of Immunology, Institutes of Biology and Medical Sciences, Soochow University Medical College, Soochow University, Suzhou, P. R. China;Department of Pathology, Institutes of Biology and Medical Sciences, Soochow University Medical College, Soochow University, Suzhou P. R. China;Department of Pathology, The Frist Affiliated Hospital of Soochow University, Suzhou, P.R. China;Department of Pathology, Taicang Traditional Medicine Hospital of Jiangsu Province, Taicang, P.R. Chin;Investigative Toxicology and Pathology Laboratory, School of Public Health, Indiana University, Bloomington, IN, USA;

关键词: Chemotherapy;    doxorubicin;    nanoparticle;    hyaluronan;    cancer stem cell;    breast cancer;   

DOI  :  10.1080/10717544.2018.1507057

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY