Acidity/hydrogen peroxide-responsive PEGylated chitosan-modified polydopamine nanoparticles to realize effective photothermal conversion and intracellular drug delivery

Abstract

To realize effective photothermal conversion and intracellular drug delivery for application of cancer treatment, an acidity/hydrogen peroxide-responsive nanoparticle system comprising melanin-like polydopamine (PDA) as the hydrophobic core covered by PEGylated chitosan (PEG-CS) conjugates is created herein. The PEG-CS/PDA nanoparticles characterized with a well-dispersed spherical shape exhibited prominent colloidal stability in the milieu of physiological salt concentration. Through π- π stacking and hydrophobic interactions between doxorubicin (DOX) and PDA, DOX molecules were efficiently incorporated into the PEG-CS/PDA nanoparticles. With solution pH being adjusted from 7.4 to 5.0, the ionic complexation of protonated chitosan with negatively-charged PDA enabled the embedding of outer PEG segments of DOX@PEG-CS/PDA nanoparticles into the neutral and gel-like surfaces, thus eliciting interparticle aggregation. The same pH stimulation also accelerated DOX release due to the declined interactions of DOX and PDA combined with enhanced repulsion force between positively-charged chitosan and DOX. Notably, the PEG-CS/PDA nanoparticles not only showed robust photothermal effect and stability, but also were significantly degraded by hydrogen peroxide. After being endocytosed by TRAMP-C1 cells, the DOX@PEG-CS/PDA nanoparticles gradually released drug within acidic organelles, thus promoting drug accumulation in nuclei to kill cancer cells. This work indicates the feasibility for applying such DOX@PEG-CS/PDA nanoparticles in cancer treatment.