A comparative study of the in vitro antitumor effect of the disulfide-linked and diselenide-linked polyethylene glycol-curcumin nanoparticles

Abstract

Curcumin (CUR) is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti-cancer drug in various cancers. However, poor water solubility and low bioavailability posed a challenge for clinical application of curcumin. In this work, four CUR prodrugs, namely PEG4000-SS-CUR, PEG1500-SS-CUR, PEG4000-SeSe-CUR and PEG1500-SeSe-CUR were synthesized. These four CUR prodrugs have high CUR loading content and can self-assemble into spherical nanoparticles (NPs) with particle size of 90–190 nm in aqueous solution. The four CUR prodrug NPs exhibit good colloidal stability in PBS buffer and promoted drug release in response to GSH. Due to the enhanced water solubility, the four CUR prodrug NPs all exhibit reduced cellular uptake amount as compared to CUR in in vitro cellular uptake study. The four CUR prodrug NPs exhibit similar cytotoxicity against 22Rv1 cells as compared to free CUR while PEG4000-SeSe-CUR NPs exhibit the highest cytotoxicity and induce the highest cell apoptosis ratio against 4T1 cells in in vitro antitumor effect study. PEG4000-SeSe-CUR NPs developed in this work were proven to be an effective nanoformulation of CUR against 4T1 cells.

Graphical Abstract

Keywords:

• Curcumin
• prodrug nanoparticles
• diselenide

Additional information

Funding

This work was supported by grants from the Key Research and Development Program of Changzhou (Applied Basic Research, Grant No. CJ20210030), Guangdong Basic and Applied Basic Research Foundation (Grant No. 2022A1515010400) and Xiangshan talent project of Zhuhai People’s Hospital (Grant No. 2021XSYC-04).