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@MoS₂ (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@MoS₂ and the inhibitory effect of curcumin on P-gp.
Results: The ICG&Cur@MoS₂ NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS₂ + NIR group was significantly lower than that in ICG@MoS₂ + 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@MoS₂ NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS₂ + NIR group are significantly smaller than those in the MoS₂ + NIR group (95.0 vs 420.9 mm³, p< 0.05).
Conclusion: In conclusion, we have successfully synthesized ICG&Cur@MoS₂ 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@MoS₂ can effectively inhibit the expression of P-gp, which will enhance the PDT effect.
Keywords: P-glycoprotein, hepatocellular carcinoma, indocyanine green, curcumin, MoS₂, photothermal-photodynamic therapy