Concurrent photothermal therapy and photodynamic therapy for cutaneous squamous cell carcinoma by gold nanoclusters under a single NIR laser irradiation
Concurrent photothermal therapy and photodynamic therapy for cutaneous squamous cell carcinoma by gold nanoclusters under a single NIR laser irradiation
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单次近红外激光照射下金纳米簇对皮肤鳞状细胞癌的同步光热疗法和光动力疗法。
DOI：
10.1039/c9tb01573f
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发表时间：
2019-11-28
影响因子：
7
通讯作者：
Wang, Xiuli
中科院分区：
文献类型：
--
作者：
Liu, Pei;Yang, Weitao;Wang, Xiuli
光疗法，特别是光热疗法（Photothermal Therapy，PTT）和光动力疗法（Photodynamic Therapy，PDT），因其创伤小、疗效高、副作用小而成为治疗皮肤癌的一种有前途的治疗技术。然而，单模态疗法，PTT或PDT，在治疗皮肤癌中具有有限的临床有效性。因此，PTT和PDT的组合应用已被频繁报道;然而，PTT和PDT通常需要各自的光剂和激发光源，从而导致临床转化的挑战。在这项研究中，为了解决这些问题，我们报告了使用生物相容性金纳米团簇Au 25（Capt）18，使用808 nm近红外（NIR）激光同时进行皮肤鳞状细胞癌（cSCC）的PTT和PDT治疗。利用其高的光热转换效率、有效的单线态氧产生和强的光热稳定性，Au 25（Capt）18纳米簇增强了体外cSCC XL 50细胞的显著增殖抑制和体内SKH-1小鼠的cSCC肿瘤的抑制。特别是，在808 nm光照射下，PTT和PDT的肿瘤细胞杀伤贡献估计分别为28.86%和71.14%，通过使用ROS清除剂来淬灭PDT效应。在一个疗程的同时PTT和PDT后观察到肿瘤浸润的CD 4 + T和CD 8 + T细胞。初步的毒性研究表明Au 25（Capt）18纳米团簇的低副作用。通过这项研究，我们报告了使用一个简单的纳米结构，同时PTT和PDT的应用，以有效地杀死cSCC和诱导抗肿瘤免疫反应。我们的研究可能会导致开发有效的光剂，用于当前协同应用不同的光疗法，具有靶向免疫反应，用于治疗癌症。
Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has become a promising therapeutic technique for the treatment of skin cancers because of its minial invasiveness, high efficacy, and low side effects. Nevertheless, single modality therapy, either PTT or PDT, has limited clinical effectiveness in treating skin cancers. Thus, combined applications of PTT and PDT have been frequently reported; however, PTT and PDT often require their respective photoagents and excitation light sources, resulting in challenges in clinical transformation. In this study, to address these issues, we report the use of biocompatible gold nanoclusters Au25(Capt)18 for the concurrent PTT and PDT treatment of cutaneous squamous cell carcinoma (cSCC) using an 808 nm near-infrared (NIR) laser. Utilizing their high light-thermal conversion efficiency, potent generation of singlet oxygen, and strong photothermal stability, Au25(Capt)18 nanoclusters potentiated a significant proliferation suppression of cSCC XL50 cells in vitro and the inhibition of cSCC tumors on SKH-1 mice in vivo. In particular, under 808 nm light irradiation, the tumor-cell-killing contributions of PTT and PDT were estimated to be 28.86% and 71.14%, respectively, by using an ROS scavenger to quench the PDT effect. Tumor-infiltrating CD4+ T and CD8+ T cells were observed after one course of concurrent PTT and PDT. Preliminary toxicity studies indicated low adverse effects of the Au25(Capt)18 nanoclusters. Through this study, we report the use of a simple nanostructure for simultaneous PTT and PDT applications to effectively kill cSCC and to induce anti-tumor immune responses. Our study could lead to the development of effective photoagents for current, synergistic applications of different phototherapies with targeted immunological responses for the treatment of cancers.