Enhanced Photothermal-Photodynamic Therapy by Indocyanine Green and Curcumin-Loaded Layered MoS(2) Hollow Spheres via Inhibition of P-Glycoprotein

PURPOSE: P-glycoprotein (P-gp), which is highly expressed in liver cancer cells, is one of the obstacles for the treatment of cancer. In this study, we have prepared and characterized a kind of novel ICG&Cur@MoS(2) (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely. METHODS: In this work, plenty of studies including drug release, acute toxicity, Western blot, real-time PCR, cell viability, therapeutic experiment in vivo, immunofluorescence and so on were conducted to test the antitumor potential of ICG&Cur@MoS(2) and the inhibitory effect of curcumin on P-gp. RESULTS: The ICG&Cur@MoS(2) NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS(2) + NIR group was significantly lower than that in ICG@MoS(2) + NIR group (75.3% vs 81.2%, 59.0% vs 64.4%, 20.3% vs 27.5%, and 15.4% vs 22.3%) at the concentration of ICG at 0.5, 5, 25, 50 μg/mL (P<0.05 at each concentration). Western blot, Q-PCR, and immunofluorescence assay indicate ICG&Cur@MoS(2) NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS(2) + NIR group are significantly smaller than those in the MoS(2) + NIR group (95.0 vs 420.9 mm(3), p<0.05). CONCLUSION: In conclusion, we have successfully synthesized ICG&Cur@MoS(2) nanoparticles which can not only achieve PTT-PDT but also inhibit P-gp effectively. Our findings indicate that the PTT-PDT exhibits great potential in the treatment of hepatocellular carcinoma. Meanwhile, ICG&Cur@MoS(2) can effectively inhibit the expression of P-gp, which will enhance the PDT effect.