Enhanced Antitumor Efficacy and Reduced Systemic Toxicity of Sulfatide-Containing Nanoliposomal Doxorubicin in a Xenograft Model of Colorectal Cancer
Files
File version
Author(s)
Yu, Yan
Shigdar, Sarah
Fang, Ding Zhi
Du, Jun Rong
Wei, Ming Q
Danks, Andrew
Liu, Ke
Duan, Wei
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
1991907 bytes
File type(s)
application/pdf
Location
Abstract
Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX), a sulfatide-containing liposome (SCL) encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX) using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.
Journal Title
PloS One
Conference Title
Book Title
Edition
Volume
7
Issue
11
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2012 Lin et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
Item Access Status
Note
Access the data
Related item(s)
Subject
Medical and Health Sciences not elsewhere classified