VEGFR2-targeted NIR-II fluorescent probe for precise imaging and surgical navigation of ovarian cancer.

Molecular imaging of tumor biomarkers represents a crucial direction for advancing precision cancer diagnosis and therapy. As a core regulator of tumor angiogenesis, VEGFR2 represents an ideal molecular imaging target. Herein, a novel VEGFR2-targeting peptide (HTMYYHHYQHHLSSSDICLPRWGCLWED, named as VTP) was designed and synthesized by conjugating a peptide K237 (HTMYYHHYQHHL), a flexible tripeptide linker (Ser-Ser-Ser, SSS), and an albumin-binding peptide (ABP, DICLPRWGCLWED). The surface plasmon resonance (SPR) analysis confirmed that VTP had high binding affinity for VEGFR2 (KD = 15.4 nM).

Although indocyanine green (ICG) has been widely used in clinical practice, its short half-life and lack of active targeting ability significantly restrict its potential for intraoperative navigation. In this study, the VEGFR2-targeting peptide VTP was conjugated with ICG to successfully construct a targeted fluorescent probe, ICG-VTP. Owing to ABP modification, this probe exhibits a longer blood half-life and shows accumulation characteristics that are highly positively correlated with VEGFR2 expression levels in multiple tumor models, including ovarian cancer, colorectal cancer, and non-small cell lung cancer. The probe yielded tumor-to-background ratios (TBR) of 2.95, 2.05, and 1.42 in high (SKOV3), moderate (HCT116), and low (A549) VEGFR2-expressing tumors at 10 h post-injection, respectively, confirming its specificity for VEGFR2 imaging.

Further, the ICG-VTP probe enabled successful intraoperative fluorescence navigation and precise tumor resection. Safety assessments revealed no significant toxicity at cellular or tissue levels.

In summary, the ICG-VTP probe demonstrates strong specificity and superior imaging contrast of VEGFR2-positive tumors, underscoring its high potential to advance biomedical research and clinical translation.