Light‐triggered dePEGylation with decreasing the diameter of hydroxyapatite nanocarriers for enhanced cellular uptake and tumor penetration

Abstract

Abstract PEGylation of nano‐drug delivery systems (NDDSs) has been investigated to overcome the side effect of conventional chemotherapy including improving pharmacokinetics by prolonging drug circulation, reducing immune clearance and premature drug leakage. Although, PEGylation of NDDSs can also disturb the tumor penetration and cellular uptake with the diameter enhancement. Therefore, in this work, we constitute a light‐triggered dePEGylation strategy, which results in the decrease of diameter of the pH‐responsive hydroxyapatite drug nanocarriers (DOX@HAP‐PEG) for enhanced cellular uptake and tumor penetration. Under light irradiation (650 nm), PEG chains can be availably separated from the nanocarrier by cleaving the Cy linker. Moreover, the cellular uptake of DOX@HAP‐PEG and DOX@HAP‐PEG+L (DOX@HAP‐PEG under light irradiation) are explored against MCF‐7, Hela, and HepG2 cancer cells. The results show that the cellular uptake of DOX@HAP‐PEG is lower than that of DOX@HAP‐PEG+L. In addition, in 3D tumor model, DOX@HAP‐PEG+L can better penetrate into the cell spheroid than DOX@HAP‐PEG, which is demonstrated by the accumulated fluorescence signals in the cell spheroid.

Keywords

• dePEGylation
• hydroxyapatite
• light‐responsiveness
• particle size change
• tumor penetration