Functionalized N-hydroxypropyl trimethylammonium chloride chitosan as an ICG/DOX co-delivery nanocarriers for targeted and chemo-photothermal combination therapy

Doxorubicin (DOX) is considered one of the most effective chemotherapy drugs and is used as a first-line drug for many cancers. However, it has shown serious side effects such as cardiotoxicity and colonic ulcers, which limit its clinical use. Targeted delivery to tumor cells by nanocarriers or decreasing DOX dosage is considered to be an effective way to reduce the toxic and side effects of DOX on normal human tissues. In this paper, the mannose-functionalized N-2-HACC nanoparticles (MN NPs) loaded with DOX and Indocyanine Green (ICG) (DOX/ICG@MN NPs) were synthesized by the ion-crosslinking method, which were used for the in vitro targeted photothermal and chemical therapy. The results of FT-IR, particle size analysis, and SEM showed that ICG and DOX were successfully loaded, and DOX/ICG@MN NPs had great dispersibility and size. The results of the cell safety test showed that MN NPs had good safety. The photothermal stability tests revealed that the ICG in DOX/ICG@MN NPs had excellent thermal stability and photothermal conversion efficiency than the free ICG. The DOX release of DOX/ICG@MN NPs is pH-responsive, which promoted the effective release in slightly acidic environments at the tumor site. Owing to the specific targeting ability of mannose, DOX/ICG@MN NPs could be effectively uptake into HCT116 cells. In the presence of Near-Infrared irradiation (NIR), DOX/ICG@MN NPs exhibited synergistic treatment effects against tumor cells, which could significantly reduce the dosage of DOX and reduce the toxic side-effects on normal tissues. Therefore, this co-delivery system is considered to have significant potential for targeting tumors and chemo-photothermal therapy.