Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release

Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine. - Graphical abstract: pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated by desolvation with chemical crosslinking, followed by electrostatic adsorbing DOX to afford DOX loaded keratin nanoparticles (KDNPs). Drug delivery profiles showed that KDNPs exhibited pH and GSH dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting NO release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine. - Highlights: • KDNPs exhibit pH and GSH dual-responsive characters. • KDNPs perform surface negative-to-positive charge conversion and accumulation at the tumor region through EPR effect. • KDNPs promote NO release from endogenous donor of S-nitrosoglutathione in the presence of GSH