Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang 110001, Liaoning, People's Republic of China.
Department of Pain Medicine, The First Hospital of China Medical University, Shenyang 110001, Liaoning, People's Republic of China.
Int J Nanomedicine. 2021 Jan 15;16:433-442. doi: 10.2147/IJN.S275938. eCollection 2021.
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 (ICG and Cur represent indocyanine green and curcumin, respectively) nanoplatform, which can achieve photothermal-photodynamic therapy and inhibit the P-gp effectively and safely.
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 and the inhibitory effect of curcumin on P-gp.
The ICG&Cur@MoS NPs exhibit an excellent photothermal effect and relatively low toxicity. Cell viability in the ICG&Cur@MoS + NIR group was significantly lower than that in ICG@MoS + 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 NPs can inhibit the P-gp effectively and safely. In vivo, the tumors in the ICG@MoS + NIR group are significantly smaller than those in the MoS + NIR group (95.0 vs 420.9 mm, p<0.05).
In conclusion, we have successfully synthesized ICG&Cur@MoS 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 can effectively inhibit the expression of P-gp, which will enhance the PDT effect.
多药耐药蛋白（P-gp）在肝癌细胞中高度表达，是癌症治疗的障碍之一。在本研究中，我们制备并表征了一种新型的 ICG&Cur@MoS（ICG 和 Cur 分别代表吲哚菁绿和姜黄素）纳米平台，该平台可以安全有效地实现光热-光动力治疗，并抑制 P-gp。
在这项工作中，进行了大量的研究，包括药物释放、急性毒性、Western blot、实时 PCR、细胞活力、体内治疗实验、免疫荧光等，以测试 ICG&Cur@MoS 的抗肿瘤潜力和姜黄素对 P-gp 的抑制作用。
ICG&Cur@MoS NPs 表现出优异的光热效应和相对较低的毒性。在 ICG@MoS + NIR 组中，ICG 浓度为 0.5、5、25、50μg/mL 时，细胞活力分别显著低于 ICG@MoS + NIR 组（75.3%比 81.2%，59.0%比 64.4%，20.3%比 27.5%，15.4%比 22.3%）（各浓度时 P<0.05）。Western blot、Q-PCR 和免疫荧光分析表明，ICG&Cur@MoS NPs 可以安全有效地抑制 P-gp。在体内，ICG@MoS + NIR 组的肿瘤明显小于 MoS + NIR 组（95.0 比 420.9 mm，p<0.05）。
总之，我们成功合成了 ICG&Cur@MoS 纳米粒子，不仅可以实现 PTT-PDT，还可以有效抑制 P-gp。我们的研究结果表明，PTT-PDT 在肝癌治疗中具有巨大潜力。同时，ICG&Cur@MoS 可以有效抑制 P-gp 的表达，从而增强 PDT 效应。
