Surface-fluorinated and pH-sensitive carboxymethyl chitosan nanoparticles to overcome biological barriers for improved drug delivery in vivo.

Herein, pH-sensitive carboxymethyl chitosan (CMCS) nanoparticles with fluorinated surface modification were prepared for efficient drug delivery. N-(3-Aminopropyl)-imidazole was pre-grafted onto carboxymethyl chitosan to fabricate the pH-sensitive nanoparticles (AM NPs), then was surface-modified with perfluorobutyric anhydride to give the fluorinated nanoparticles (FM NPs). AM and FM NPs had a regular spherical structure with the size about 150-160 nm, which was kinetically stabled in the physical environment and showed pH-triggered drug release at mildly acidic conditions. A series of cell experiments verified that surface fluorination of nanoparticles could enhance cellular uptake and improve cytotoxicity in different tumor cells without the targeting recognition between host and ligands. Besides, fluorine-modified nanoparticles had longer-term blood circulation and more accumulation in tumor site, resulting in higher bioavailability and superior antitumor efficiency for anticancer drugs in vivo. These results suggested that the pH-sensitive and fluorinated nanoparticles had great potential as be efficient drug currieries for cancer chemotherapy.