One-pot fabrication of pH/reduction dual-stimuli responsive chitosan-based supramolecular nanogels for leakage-free tumor-specific DOX delivery with enhanced anti-cancer efficacy

Facile one-pot approach was established to fabricate chitosan-based supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking of the β -cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter ( D h ) of 140 nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio of carrier:DOX at 25:10. They were stable in the simulated physiological medium with premature drug release of only 3% over 60 h, while a high cumulative release up to 82.3% was achieved within 84 h in a sustained manner without initial burst in the simulated tumor intracellular micro-environment. The MTT assays indicated that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced antitumor efficacy in comparison with the free DOX.