Chitosan-based DDSs for pH/hypoxia dual-triggered DOX delivery: Facile morphology modulation for higher in vitro cytotoxicity

The morphology of the drug delivery systems (DDSs) has been recognized to play an important role in their phagocytosis, cellular interaction and distribution. However, it is a technical challenge to simply prepare the non-spherical nanoscaled DDSs. Here, a facile strategy was developed to fabricate the pH/hypoxia dual-responsive nanowires by adding the maleic acid (MAH) and PEG modified chitosan (PEG-SS-CS-MAH) into aqueous solution of DOX. Compared with the PEG-SS-CS-MAH/DOX nanoparticles (NPs) by adding DOX into the PEG-SS-CS-MAH solution, the PEG-SS-CS-MAH/DOX nanowires (NWs) possessed a higher drug loading capacity of 58% and better pH/hypoxia dual-triggered DOX release performance with higher drug release in the simulated tumor intracellular microenvironment but a much lower premature drug leakage in the simulated normal physiological medium. As a result, higher in vitro anti-tumor efficacy was achieved with the PEG-SS-CS-MAH/DOX NWs, demonstrating their promising potential for tumor chemotherapy.