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.
Keywords: Co-delivery nanoparticles; Rose Bengal; carboxymethyl chitosan; glutathione response; oral cancer; oxymatrine.