Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo

Abstract The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7 ± 4.5 nm) than bare PEG-HANPs (265.1 ± 9.5 nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions ( i.e. DOX was slowly released from nanoparticles under physiological condition (pH 7.4), whereas its release rates were much higher at mildly acidic environments ( in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.