Huang Bo-Han, Li Fang-Yu, Su Shih-Po, Chen Chiung-Tong, Chang Kuo-Wei, Yang Muh-Hwa, Chen Min-Chieh, Chiang Huihua Kenny, Chan Yang-Hsiang, Lee Yi-Jang
Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan.
J Cell Mol Med. 2025 Jan;29(1):e70324. doi: 10.1111/jcmm.70324.
The development of efficient platforms for the evaluation of anti-angiogenic agents is critical in advancing cancer therapeutics. In this study, we exploited an ultrabright semiconducting polymer dots (Pdots) integrating with a three-dimensional (3D) near-infrared-II (NIR-II) fluorescence imaging system designed to assess the efficacy of potent anti-angiogenic agents PX-478 and BPR0C261 in an oral squamous cell carcinoma (OSCC) tumour model, which depends on angiogenesis for dissemination. PX-478, a hypoxia-inducible factor-1α (HIF-1α) inhibitor, and BPR0C261, a microtubule-disrupting agent, were administrated into tumour-bearing mice established using murine MTCQ1 tongue cancer cells through intraperitoneal injection and oral gavage, respectively. Our findings showed that PX-478 and BPR0C261 significantly inhibited tumour growth and extended the life span of tumour-bearing mice without decreasing the body weights. The Pdots-based NIR-II vascular imaging demonstrated that the tumour vascularity was suppressed by PX-478 and BPRC0261. Accordingly, the excised tumours treated with anti-angiogenic agents showed less blood vessels than that treated with vehicles. The expression of endothelial markers CD31 was also found to be reduced in tumours treated with PX-478 and BPRC0261 using immunohistochemical (IHC) staining and Western blot analysis. Furthermore, PX-478 could suppress the expression of HIF-1α and vascular endothelial growth factor-A (VEGF-A), but BPRC0261 only suppressed VEGF-A. Taken together, this innovative 3D NIR-II imaging system combining the biocompatible Pdots with unique optical specificity enables non-invasive, real-time monitoring the efficacy of anti-angiogenic compounds.
开发高效的抗血管生成药物评估平台对于推进癌症治疗至关重要。在本研究中，我们利用了一种超亮半导体聚合物点（Pdots），其与三维（3D）近红外二区（NIR-II）荧光成像系统相结合，旨在评估强效抗血管生成药物PX-478和BPR0C261在口腔鳞状细胞癌（OSCC）肿瘤模型中的疗效，该模型的扩散依赖于血管生成。PX-478是一种缺氧诱导因子-1α（HIF-1α）抑制剂，BPR0C261是一种微管破坏剂，分别通过腹腔注射和灌胃给药于使用鼠MTCQ1舌癌细胞建立的荷瘤小鼠。我们的研究结果表明，PX-478和BPR0C261显著抑制肿瘤生长并延长荷瘤小鼠的寿命，且不降低体重。基于Pdots的NIR-II血管成像表明，PX-478和BPRC0261可抑制肿瘤血管生成。因此，用抗血管生成药物治疗的切除肿瘤显示出比用载体治疗的肿瘤血管更少。使用免疫组织化学（IHC）染色和蛋白质印迹分析还发现，在用PX-478和BPRC0261治疗的肿瘤中，内皮标志物CD31的表达降低。此外，PX-478可抑制HIF-1α和血管内皮生长因子-A（VEGF-A）的表达，但BPRC0261仅抑制VEGF-A。综上所述，这种将生物相容性Pdots与独特光学特异性相结合的创新3D NIR-II成像系统能够无创、实时监测抗血管生成化合物的疗效。
