Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, United States of America.
Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States of America.
Nanotechnology. 2022 Aug 31;33(47). doi: 10.1088/1361-6528/ac893a.
Bladder cancer has been ranked as one of the most commonly occurring cancers in men and women with approximately half of the diagnoses being the late stage and/or metastatic diseases. We have developed a novel cancer treatment by combining gold nanostar-mediated photothermal therapy with checkpoint inhibitor immunotherapy to treat bladder cancer. Experiment results with a murine animal model demonstrated that our developed photoimmunotherapy therapy is more efficacious than any individual studied treatment. In addition, we used intravital optical imaging with a dorsal skinfold window chamber animal model to study immune responses and immune cell accumulation in a distant tumor following our photoimmunotherapy. The mice used have the CX3CR1-GFP receptor on monocytes, natural killer cells, and dendritic cells allowing us to dynamically track their presence by fluorescence imaging. Our proof-of-principle study results showed that the photoimmunotherapy triggered anti-cancer immune responses to generate anti-cancer immune cells which accumulate in metastatic tumors. Our study results illustrate that intravital optical imaging is an efficient and versatile tool to investigate immune responses and mechanisms of photoimmunotherapy in future studies.
膀胱癌已被列为男性和女性中最常见的癌症之一,大约一半的诊断为晚期和/或转移性疾病。我们通过将金纳米星介导的光热疗法与检查点抑制剂免疫疗法相结合,开发了一种新型的癌症治疗方法,用于治疗膀胱癌。使用小鼠动物模型的实验结果表明,我们开发的光免疫疗法比任何单独研究的治疗方法都更有效。此外,我们使用带有背部皮肤窗室动物模型的活体光学成像技术,研究了我们的光免疫疗法后远处肿瘤中的免疫反应和免疫细胞积累。我们使用的小鼠在单核细胞、自然杀伤细胞和树突状细胞上具有 CX3CR1-GFP 受体,这使我们能够通过荧光成像动态跟踪它们的存在。我们的原理验证研究结果表明,光免疫疗法引发了抗癌免疫反应,产生了在转移性肿瘤中积累的抗癌免疫细胞。我们的研究结果表明,活体光学成像技术是一种有效的、多功能的工具,可以在未来的研究中研究免疫反应和光免疫疗法的机制。