Integrating Ultrabright Polymer Dots and Stereo NIR-II Imager for Assessing Anti-Angiogenic Drugs in Oral Cancer Model

J Cell Mol Med. 2025 Jan;29(1):e70324. doi: 10.1111/jcmm.70324.

Abstract

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.

Keywords: 3D NIR‐II fluorescence imaging system; BPR0C261; HIF‐1α; anti‐angiogenic agents; polymer dots; tumour vascularity.

MeSH terms

  • Angiogenesis Inhibitors* / pharmacology
  • Angiogenesis Inhibitors* / therapeutic use
  • Animals
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mouth Neoplasms* / diagnostic imaging
  • Mouth Neoplasms* / drug therapy
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Neovascularization, Pathologic* / drug therapy
  • Optical Imaging / methods
  • Polymers* / chemistry
  • Stilbenes
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Polymers
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • fosbretabulin
  • Stilbenes