NIR-II Fluorescence Imaging for the Detection and Resection of Cancerous Foci and Lymph Nodes in Early-Stage Orthotopic and Advanced-Stage Metastatic Ovarian Cancer Models.
Tao PuYawei LiuYuetian PeiJing PengZehua WangMing DuQiyu LiuFangfang ZhongMingxing ZhangFuyou LiCong-Jian XuXiao-Yan ZhangPublished in: ACS applied materials & interfaces (2023)
The high mortality rate of ovarian cancer can be primarily attributed to late diagnosis and early lymph node (LN) metastasis. The anatomically deep-located ovaries own intricate anatomical structures and lymphatic drainages that compromise the resolution and sensitivity of near-infrared first-window (NIR-I) fluorescence imaging. Reported NIR-II imaging studies of ovarian cancer focused on late-stage metastasis detection via the intraperitoneal xenograft model. However, given the significant improvement in patient survival associated with early-stage cancer detection, locating tumors that are restricted within the ovary is equally crucial. We obtained the polymer nanoparticles with bright near-infrared-II fluorescence (NIR-II NPs) by nanoprecipitation of DSPE-PEG, one of the ingredients of FDA-approved nanoparticle products, and benzobisthiadiazole, an organic NIR-II dye. The one-step synthesis and safe component lay the groundwork for its clinical translation. Benefiting from the NIR-II emission (∼1060 nm), NIR-II NPs enabled a high signal-to-noise (S/N) ratio (13.4) visualization of early-stage orthotopic ovarian tumors with NIR-II fluorescence imaging for the first time. Imaging with orthotopic xenograft allows a more accurate mimic of human ovarian cancer origin, thereby addressing the dilemma of translating existing nanoprobe preclinical research by providing the nano-bio interactions with early local tumor environments. After PEGylation, the desirable-sized probe (∼80 nm) exhibited high lymphophilicity and relatively extended circulation. NIR-II NPs maintained their accurate detection of orthotopic tumors, tumor-regional LNs, and minuscule (<1 mm) disseminated peritoneal metastases simultaneously (with S/N ratios all above 5) in mice with advanced-stage cancer in real time ∼36 h after systematic delivery. With NIR-II fluorescence guidance, we achieved accurate surgical staging in tumor-bearing mice and complete tumor removal comparable to clinical practice, which provides preclinical data for translating NIR-II fluorescence image-guided surgery.
Keyphrases
- fluorescence imaging
- photodynamic therapy
- lymph node
- early stage
- drug release
- high resolution
- fluorescent probe
- type diabetes
- sentinel lymph node
- air pollution
- papillary thyroid
- radiation therapy
- cardiovascular disease
- cardiovascular events
- neoadjuvant chemotherapy
- mesenchymal stem cells
- adipose tissue
- big data
- atrial fibrillation
- metabolic syndrome
- deep learning
- sensitive detection
- mass spectrometry
- highly efficient
- cell therapy
- rectal cancer
- skeletal muscle
- risk factors