A glutathione-sensitive drug delivery system based on carboxymethyl chitosan co-deliver Rose Bengal and oxymatrine for combined cancer treatment.

At present, monotherapy of tumor has not met the clinical needs, due to high doses, poor efficacy, and the emergence of drug resistance. Combination therapy can effectively solve these problems, which is a better option for tumor suppression. Based on this, we developed a novel glutathione-sensitive drug delivery nanoparticle system (OMT/CMCS-CYS-RB NPs) for oral cancer treatment. Briefly, carboxymethyl chitosan (CMCS) was used as a carrier to simultaneously load Rose Bengal (RB) and oxymatrine (OMT). The OMT/CMCS-CYS-RB NPs prepared by ion crosslinking were spheres with a stable structure. In addition, the nanoparticles can be excited in vitro to generate a large amount of singlet oxygen, which has a good photodynamic effect. In vitro anti-tumor activity study showed that the nanoparticles after the laser enhanced therapeutic efficacy on tumor cells compared with the free drug and exhibited well security. Furthermore, OMT/CMCS-CYS-RB NPs could inhibit the PI3K/AKT signaling pathway in oxidative stress, and realize tumor apoptosis through mitochondria-related pathways. In conclusion, this combination delivery system for delivering RB and OMT is a safe and effective strategy, which may provide a new avenue for the tumor treatment.