Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Sci Adv. 2018 Apr 18;4(4):eaaq1090. doi: 10.1126/sciadv.aaq1090. eCollection 2018 Apr.
Patients with high-grade serous ovarian carcinoma (HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The U.S. Food and Drug Administration-approved biomarkers for HGSC-CA-125 (cancer antigen 125) and HE4 (human epididymis protein 4)-do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease.
患有高级别浆液性卵巢癌(HGSC)的患者 5 年生存率较低,早期发现可能显著提高生存率。美国食品和药物管理局批准的 HGSC 标志物-CA-125(癌抗原 125)和 HE4(人附睾蛋白 4)-通常在疾病的晚期才在血清中出现可检测水平。放置在靠近疾病部位的植入式设备,例如在输卵管、卵巢、子宫腔或腹腔内,可能构成改善 HGSC 检测的可行策略。我们设计了一种由抗体功能化碳纳米管复合物组成的原型光学传感器,该传感器通过调制纳米管的光学带隙对 HE4 进行定量响应。该复合物以纳摩尔的灵敏度测量 HE4,以区分疾病和良性患者的生物流体。传感器被植入四种卵巢癌模型中,在半透膜内,能够在活体动物中进行 HE4 的光学检测。我们展示了第一个能够在疾病的原位模型中进行非侵入性癌症生物标志物检测的体内光学纳米传感器。