Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P. R. China.
Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, Hubei, P. R. China.
Theranostics. 2019 Jul 13;9(19):5424-5442. doi: 10.7150/thno.33015. eCollection 2019.
Photodynamic therapy (PDT) is a clinically approved and minimally invasive form of cancer treatment. However, due to hypoxia at the tumor site and phototoxicity to normal tissues, monotherapies using photosensitizers remain suboptimal. This study aimed to develop a highly selective controlled catalase-enhanced synergistic photodynamic and photothermal cancer therapy based on gold nanostars. Gold nanostars (GNS) with high thermal conversion efficiency were used as the core for photothermal therapy (PTT) and the shell consisted of the photosensitizer Ce6-loaded mesoporous silicon. The shell was modified with catalase (E), which catalyzes the conversion of hydrogen peroxide to oxygen at the tumor site, alleviating hypoxia and increasing the effect of the photodynamic treatment. Finally, a phospholipid derivative with c(RGDyK) was used as the targeting moiety and the nanoparticle-encapsulating material. The nanoprobe exhibited good dispersion, high stability, and high photothermal conversion efficiency (~28%) for PTT as well as a photodynamic "on-off" effect on Ce6 encapsulated in mesoporous channels. The "release" of Ce6 was only triggered under photothermal stimulation . Due to its targeting ability, 72 h after injection of the probe, the tumor site in mice showed an observable CT response. The combined treatment using photothermal therapy (PTT) and catalase-enhanced photo-controlled PDT exerted a superior effect to PTT or PDT monotherapies. Our findings demonstrate that the use of this intelligent nanoprobe for CT-targeted image-guided treatment of tumors with integrated photothermal therapy (PTT) and catalase-enhanced controlled photodynamic therapy (PDT) may provide a novel approach for cancer theranostics.
光动力疗法（PDT）是一种临床认可的微创癌症治疗方法。然而，由于肿瘤部位的缺氧和对正常组织的光毒性，使用光敏剂的单一疗法仍然不尽如人意。本研究旨在基于金纳米星开发一种高度选择性的控制过氧化氢酶增强协同光动力和光热癌症治疗。具有高热转换效率的金纳米星（GNS）被用作光热治疗（PTT）的核心，外壳由负载光敏剂 Ce6 的介孔硅组成。壳层用过氧化氢酶（E）修饰，在肿瘤部位催化过氧化氢转化为氧气，缓解缺氧并提高光动力治疗效果。最后，使用带有 c（RGDyK）的磷脂衍生物作为靶向部分和纳米颗粒包封材料。该纳米探针表现出良好的分散性、高稳定性和高光热转换效率（约 28%），用于 PTT 以及介孔通道中封装的 Ce6 的光动力“开-关”效应。只有在光热刺激下才会触发 Ce6 的“释放”。由于其靶向能力，在探针注射 72 小时后，小鼠的肿瘤部位显示出可观察到的 CT 反应。光热治疗（PTT）和过氧化氢酶增强光控 PDT 的联合治疗对 PTT 或 PDT 单一疗法表现出优越的效果。我们的研究结果表明，使用这种智能纳米探针进行 CT 靶向成像引导治疗，结合光热治疗（PTT）和过氧化氢酶增强的控制光动力治疗（PDT），可能为癌症治疗提供一种新方法。
