Dimethylcurcumin-loaded methoxypolyethylene glycol-dimethylcurcumin conjugate nanoparticles: preparation, characterization and in vitro antitumor study

Dimethylcurcumin (DMC) is a synthetic curcuminoid which can enhance androgen receptor (AR) degradation to suppress AR-associated cancers. However, the poor water solubility and low bioavailability of DMC limit its biomedical applications. In our study, a water-soluble methoxypolyethylene glycol-dimethylcurcumin conjugate (cDMC-mPEG) was synthesized and further used for preparation of DMC loaded nanoparticles for effective DMC delivery. cDMC-mPEG was synthesized and characterized by proton nuclear magnetic resonance, fourier transform infrared spectroscopy, ultraviolet–visible spectroscopy, thermogravimetric analysis and differential scanning calorimetry. cDMC-mPEG self-assemble into nanoparticles in aqueous solution and can be used to encapsulate free DMC to form DMC-loaded cDMC-mPEG nanoparticles with small sizes and spherical morphology. The in vitro drug release study shows that DMC@cDMC-mPEG (15.3%) nanoparticles exhibit pH-triggered DMC release behaviors. The cellular uptake study shows that cDMC-mPEG and DMC@cDMC-mPEG (15.3%) nanoparticles exhibit enhanced cellular uptake as compared to free DMC, and DMC@cDMC-mPEG (15.3%) nanoparticles exhibit the highest cellular uptake amount. As a result, DMC@cDMC-mPEG (15.3%) nanoparticles exhibit enhanced cytotoxicity against 22Rv1 cells as compared to cDMC-mPEG and free DMC in in vitro antitumor effect study. The DMC@cDMC-mPEG (15.3%) nanoparticles developed in this work provide an effective nano-formulation for anti-prostate cancer DMC delivery.