Fabrication of a pH responsive DOX conjugated PEGylated palladium nanoparticle mediated drug delivery system: an in vitro and in vivo evaluation

Abstract

Efficient delivery of therapeutics into tumor cells to increase the intracellular drug concentration is one of the key issues in cancer therapy. In this work, we designed pH responsive PEGylated palladium nanoparticles (PdNPs) as an anticancer drug nanocarrier system for effective drug delivery. The synthesis of the nanocarrier involved conjugation of doxorubicin (DOX) to the surface of PEGylated PdNPs via a hydrazone interaction. The nanoparticles were characterized by UV-spectroscopy, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), zeta potential, Fourier transmission Infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Nuclear Magnetic Resonance (NMR). The drug release behavior was subsequently studied at different pH conditions. The results showed a sustained release of DOX preferentially at the desired endosomal pH (5.5). The biological activity of the DOX conjugated PEGylated PdNPs was studied by an MTT assay, fluorescence microscopy, and apoptosis. Intracellular-uptake studies revealed preferential uptake of these NPs into HeLa cancer cells. The in vitro apoptosis study revealed that the DOX conjugated PEGylated PdNPs caused significant death to the HeLa cells. Further, blank PEGylated PdNPs displayed low toxicity and good biocompatibility. DOX conjugated PEGylated PdNPs had the strongest anti-tumor efficacy against HeLa tumor xenograft models in vivo. These findings demonstrated that PEGylated PdNPs were deemed as a potential drug nanocarrier for cancer therapy.