Abstract

Chemotherapy using vascular targeting agents is an emerging new approach for cancer therapy. Combretastatin A4 (CA4) is a leading vascular-disrupting agent that targets the tumor blood vasculature for clinical tumor elimination. However, the extremely poor water solubility of CA4 hinders its biomedical applications. In this study, nanoparticles composed of novel PEGylated alternating copolymer-CA4 conjugates are designed to improve the therapeutic efficiency of CA4. First, an alternating copolymer with an alkene-pendant is synthesized by mPEG-OH-initiated ring-opening copolymerization. Then, side carboxyl groups are introduced by a thio-ene "click" chemical reaction, followed with CA4 conjugation through the Yamaguchi-reaction, resulting in the target copolymer, mPEG-b-P(PA-alt-GCA4). Interestingly, the polymer-drug conjugates can self-assemble into nanoparticles with an average diameter of 55.6nm. The in vitro drug release and cytotoxicity of the obtained CA4-NPs toward 4T1 cells are investigated. Finally, the antitumor efficiency is evaluated in a 4T1-tumor bearing murine model. The in vivo test results demonstrate that CA4-NPs inhibited tumor growth much more efficiently at doses of 30 and 60mg kg-1 , compared with the control group.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.