Engineering Research Center of Molecular- and Neuro-Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710026, China.
ACS Biomater Sci Eng. 2022 May 9;8(5):1892-1906. doi: 10.1021/acsbiomaterials.1c01311. Epub 2022 Apr 11.
Organic near-infrared fluorescent dye mediated photothermal therapy (PTT) and photodynamic therapy (PDT) suffer from heat shock response, since, heat shock proteins (HSPs) are overexpressed and can repair the proteins damaged by PTT and PDT. Starvation therapy by glucose oxide (GOx) can inhibit the heat shock response by limiting the energy supply. However, the delivery of sufficient and active GOx remains a challenge. To solve this problem, we utilize liposomes as drug carriers and prepare GOx loaded liposome (GOx@Lipo) with a high drug loading content (12.0%) and high enzymatic activity. The successful delivery of GOx shows excellent inhibition of HSPs and enhances PTT and PDT. Additionally, we apply the same liposome formulation to load near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbo cyanine iodide (DiR) and prepare DiR contained liposomes (DiR@Lipo) for PTT and PDT. The liposomal formulation substantially enhances the PTT and PDT properties of DiR as well as the cellular uptake and tumor accumulation. Finally, the combination therapy shows excellent tumor inhibition on 4T1 tumor-bearing mice. Interestingly, we also find that the starvation therapy can efficiently inhibit tumor metastasis, which is probably due to the immunogenic effect. Our work presents a biocompatible and effective carrier for the combination of starvation therapy and phototherapy, emphasizing the importance of auxiliary starvation therapy against tumor metastasis and offering important guidance for clinical PTT and PDT.
有机近红外荧光染料介导的光热治疗（PTT）和光动力治疗（PDT）受到热休克反应的影响，因为热休克蛋白（HSPs）过度表达，可以修复 PTT 和 PDT 损伤的蛋白质。葡萄糖氧化酶（GOx）的饥饿疗法可以通过限制能量供应来抑制热休克反应。然而，输送足够和活性的 GOx 仍然是一个挑战。为了解决这个问题，我们利用脂质体作为药物载体，并制备具有高药物载量（12.0%）和高酶活性的负载 GOx 的脂质体（GOx@Lipo）。GOx 的成功递送显示出对 HSPs 的优异抑制作用，并增强了 PTT 和 PDT。此外，我们应用相同的脂质体制剂来装载近红外染料 1,1'-二辛基-3,3,3',3'-四甲基吲哚碳菁碘化物（DiR），并制备负载 DiR 的脂质体（DiR@Lipo）用于 PTT 和 PDT。脂质体制剂大大增强了 DiR 的 PTT 和 PDT 性能以及细胞摄取和肿瘤积累。最后，联合治疗在 4T1 荷瘤小鼠上显示出优异的肿瘤抑制作用。有趣的是，我们还发现饥饿疗法可以有效地抑制肿瘤转移，这可能是由于免疫原性效应。我们的工作为饥饿疗法和光疗的联合提供了一种生物相容性和有效的载体，强调了辅助饥饿疗法对抗肿瘤转移的重要性，并为临床 PTT 和 PDT 提供了重要指导。
