Redox-responsive nanoreservoirs based on collagen end-capped mesoporous hydroxyapatite nanoparticles for targeted drug delivery

Abstract

Mesoporous hydroxyapatite (MHAp) nanoparticles have great potential in nanoscaled delivery devices due to their excellent biocompatibility, nontoxicity and high surface areas. In order to achieve targeting based on cell-specific recognition and site directed, timed and quantitatively controlled drug release to malignant cells, redox-responsive nanoreservoirs based on MHAp (LA-Col-S-S-MHAp) were fabricated by using lactobionic acid-conjugated collagen (LA-Col) as a cap, disulfide bonds as intermediate linkers and MHAp as nanoreservior. Lactobionic acid (LA) molecules acted as the targeting moiety to achieve the targeted drug delivery. The results of scanning electron microscopy (SEM), transmission electron microscopy (TEM), Brunauer–Emmett–Teller (BET), Barett–Joyner–Halenda (BJH), Fourier transform infrared spectroscopy (FTIR) and zeta potential measurements confirmed the successful preparation of LA-Col-S-S-MHAp step-by-step. Dithiothreitol (DTT) was used as an external stimulus to trigger the redox-responsive release of the drug in order to investigate the controlled release behavior of LA-Col-S-S-MHAp. The result proved that LA-Col-S-S-MHAp nanocomposite has a good end-capping efficiency of the drug under physiological conditions, and it has a characteristic of rapid response and burst drug release when exposed to reducing conditions. Confocal laser scanning microscopy (CLSM) images and flow cytometry assay demonstrated that LA-Col-S-S-MHAp nanoparticles were endocytosed and located in the cytoplasm of cells. Redox-responsive targeted drug delivery could be achieved within cells. The system affords references and ideas for designing novel stimuli responsive nanoreservoir to the clinical therapy of liver cancer.