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Temperature-dependent cell death patterns induced by functionalized gold nanoparticle photothermal therapy in melanoma cells

Yujuan ZhangJiangxi Normal UniversityXuelin ZhanJiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, ChinaJuan XiongDepartment of Preventive Medicine, School of Medicine, Shenzhen University, Shenzhen, ChinaShanshan PengJiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, ChinaWei HuangInstitute of immunotherapy and College of Basic Medicine of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, ChinaRakesh Kumar JoshiDepartment of Surgery, Pathology and Oncology, University of Western Ontario, London, CanadaYing CaiInstitute of immunotherapy and College of Basic Medicine of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, ChinaYanling LiuJiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, ChinaRong LiInstitute of immunotherapy and College of Basic Medicine of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, ChinaKeng YuanJiangxi Provincial Key Laboratory of Immunotherapy, Nanchang, ChinaNanjin ZhouInstitute of immunotherapy and College of Basic Medicine of Nanchang University, and Jiangxi Academy of Medical Sciences, Nanchang, ChinaWei‐Ping MinDepartment of Surgery, Pathology and Oncology, University of Western Ontario, London, Canada. [email protected]

2018en

ABI

Annotatsiya

Photothermal therapy (PTT) is a promising approach for cancer targeting therapy. However, the temperature-dependent killing of tumor cells in PTT remains unclear. In this study, we report necroptosis plays a role in the anti-tumor effects observed in gold nanorod (GNR)-mediated PTT in melanoma. We first synthesized gold nanorods with a targeting adaptor FA (GNRs-FA), which achieved high efficacy of targeted delivery to melanoma cells. We further demonstrated PTT, precipitated by GNRs-FA under the induction of near-infrared laser, was temperature-dependent. Furthermore, the photothermal killing of melanoma cells showed different patterns of cell death depending on varying temperature in PTT. In a lower temperature at 43 °C, the percentages of apoptosis, necroptosis and necrosis of tumor cells were 10.2%, 18.3%, and 17.6%, respectively, suggesting the cell killing is ineffective at lower temperatures. When the temperature increased to 49 °C, the cell death pattern switched to necrosis dominant (52.8%). Interestingly, when the PTT achieved a moderate temperature of 46 °C, necroptosis was significantly increased (35.1%). Additionally, GNRs-FA/PPT-mediated necroptosis was regulated by RIPK1 pathway. Taken together, this study is the first to demonstrate that temperature-dependent necroptosis is an important mechanism of inducing melanoma cell death in GNR-mediated PTT in addition to apoptosis and necrosis.

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DOI: 10.1038/s41598-018-26978-1

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