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

Abstract

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-NH2, 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 (PEG2000-MPDA@ICG&DMC and PEG5000-MPDA@ICG&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. PEG2000-MPDA@ICG&DMC and PEG5000-MPDA@ICG&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.