Ionically crosslinked alginate-based nanohydrogels for tumor-specific intracellular triggered release: Effect of chemical modification

A facile one-pot approach has been developed to prepare novel pH-responsive ionic nanohydrogels with high drug-loading capacity and desirable size for tumor-specific intracellular triggered release of anticancer drug DOX, in which the ionic crosslinking of alginate (AL) or its derivatives (oxidized alginate (OAL) or PEGylated OAL (mPEG-OAL)) and the DOX-loading ocurred simultaneously. It was found that the modification was benificial to the formation of the DOX-loaded ionic nanohydrogels with smaller diameter and narrower size distribution, even with similar DOX loading capacity. Especially for the mPEG-OAL, the resultant mPEG-OAL/DOX ionic nanohydrogels showed a hydrodynamic diameter of 135 nm with very narrow size distribution. All the three DOX-loaded ionic nanohydrogels (AL/DOX, OAL/DOX, and mPEG-OAL/DOX) showed the pH-responsive characteristic, and the last one exhibited the best capacity for controlled release, in a sustained release mode.