Department of Bioengineering, University of California, Riverside, 900 University Avenue, Riverside, CA, 92521, USA.
Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Ann Biomed Eng. 2021 Feb;49(2):548-559. doi: 10.1007/s10439-020-02589-8. Epub 2020 Aug 6.
Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Identification and removal of all ovarian intraperitoneal tumor deposits during the intraoperative surgery is important towards preventing cancer recurrence and ultimately improving patient survival. Herein, we investigate the effectiveness of virus mimicking nanoparticles, derived from genome-depleted plant-infecting brome mosaic virus, and doped with near infrared (NIR) brominated cyanine dye BrCy106-NHS, for targeted NIR fluorescence imaging of intraperitoneal ovarian tumors. We refer to these nanoparticles as optical viral ghosts (OVGs). We functionalized the OVGs with antibodies against HER2 receptor, a biomarker over-expressed in ovarian cancers. We injected functionalized OVGs, non-functionalized OVGs, and non-encapsulated BrCy106-NHS intravenously in mice implanted with ovarian intraperitoneal tumors. Tumors were extracted at 2, 6, and 24 h post-injection, and quantitatively analyzed using NIR fluorescence imaging. Fluorescence emission from tumors associated with the injection of the functionalized OVGs continued to increase between 2 and 24 h post-injection. At 24 h timepoint, the average spectrally-integrated fluorescence emission from homogenized tumors containing functionalized-OVGs was about 3.5 and 19.5 times higher than those containing non-functionalized OVGs or non-encapsulated BrCy106-NHS, respectively. Similarly, by using the functionalized-OVGs, the imaging signal-to-noise ratio at 24 h timepoint was enhanced by approximately threefold and sevenfold as compared to non-functionalized OVGs and the non-encapsulated dye, respectively. These functionalized virus-mimicking NIR nano-constructs could potentially be used for intraoperative visualization of ovarian tumors implants.
卵巢癌是影响女性生殖系统最致命的恶性肿瘤。在术中手术中识别和清除所有卵巢腹腔内肿瘤沉积物对于预防癌症复发并最终提高患者生存率非常重要。在这里，我们研究了源自基因组缺失的植物感染 Bromus mosaic 病毒的病毒模拟纳米粒子，并用近红外（NIR）溴化氰染料 BrCy106-NHS 掺杂，用于靶向腹腔内卵巢肿瘤的 NIR 荧光成像的有效性。我们将这些纳米颗粒称为光学病毒幽灵（OVG）。我们用针对 HER2 受体的抗体对 OVG 进行功能化，HER2 受体是卵巢癌中过度表达的生物标志物。我们将功能化的 OVG、非功能化的 OVG 和非包裹的 BrCy106-NHS 静脉内注射到植入卵巢腹腔内肿瘤的小鼠中。在注射后 2、6 和 24 小时提取肿瘤，并使用 NIR 荧光成像进行定量分析。与注射功能化 OVG 相关的肿瘤荧光发射在注射后 2 至 24 小时之间继续增加。在 24 小时时间点，含有功能化 OVG 的均质化肿瘤的平均光谱积分荧光发射比含有非功能化 OVG 或非包裹的 BrCy106-NHS 的肿瘤分别高约 3.5 和 19.5 倍。同样，与非功能化的 OVG 和非包裹的染料相比，使用功能化的 OVG，在 24 小时时间点的成像信号与噪声比分别提高了约三倍和七倍。这些功能化的病毒模拟近红外纳米结构有可能用于术中可视化卵巢肿瘤植入物。
