Polyethylene glycol-modified mesoporous polydopamine nanoparticles co-loaded with dimethylcurcumin and indocyanine green for combination therapy of castration-resistant prostate cancer

Herein, polyethylene glycol-modified mesoporous polydopamine (PEG-MPDA) nanoparticles co-loaded with indocyanine green (ICG) and dimethylcurcumin (ASC-J9, DMC) were developed for combination therapy of castration-resistant prostate cancer. MPDA nanoparticles were prepared and surface modified with methoxypolyethylene glycol amine (mPEG-NH 2 , M.W. 2000 and 5000). The prepared PEG2000-MPDA and PEG5000-MPDA nanoparticles were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM). ICG and DMC co-loaded PEG2000-MPDA and PEG5000-MPDA nanoparticles ( [email protected] &DMC and [email protected] &DMC) were prepared by a solvent diffusion method. The decrease in drug feeding ratios results in decline in drug loading content and increase in drug encapsulation rate. [email protected] &DMC and [email protected] &DMC nanoparticles with relatively high drug loading content (ICG 10.0 ± 0.5% and 9.2 ± 0.3%, DMC 6.7 ± 0.2% and 6.4 ± 0.3%) were selected for further studies. The hydrodynamic diameters of these two nanoparticles are between 200 and 300  nm . These two nanoparticles display enhanced stability of ICG in aqueous solution, near-infrared (NIR) laser irradiation-promoted DMC release, efficient photothermal effect, enhanced cellular uptake, and excellent biocompatibility . In in vitro antitumor effect study, these two nanoparticles exhibit enhanced antitumor effect against 22Rv1 cells as compared to ICG&DMC mixture upon 808 nm laser irradiation. Western blot analyses indicate that these two nanoparticles enhance the degradation of androgen receptor (AR) significantly. This work provides a novel strategy and an effective co-delivery system for combinational castration-resistant prostate cancer therapy.