Glioblastoma is a highly malignant
brain tumor with poor prognosis and survival rate because of a lack of effective diagnostic methods. Hydrocyanines are a type of
reactive oxygen species (ROS)-responsive
fluorescent probes, allowing for distinguishing
tumor cells from normal cells based on their different intracellular levels of ROS. However, their diagnostic applications for
glioblastoma have been limited because of the inability to discriminate between
tumor cells and other tissues with high ROS production, leading to high false-positive diagnosis. Therefore,
tumor-responsive and -specific hydrocyanines with cooperative targeting ability have great potential for improving the diagnosis and treatment of
glioblastoma.
Integrin αvβ3 plays a critical role in the progression and angiogenesis of
glioblastoma and has become a promising target for diagnosing
glioblastoma. Herein, we identify a specific
peptide ligand for
integrin αvβ3, Arg-Trp-(d-Arg)-Asn-Arg (RWrNR), which shows high binding affinity to human
glioblastoma U87MG cells. Importantly, hydro-Cy5-RWrNR conjugation allowed for distinguishing U87MG cells from normal cells in response to intracellular ROS. Particularly, hydro-Cy5-RWrNR could not only selectively accumulate in orthotopic U87MG
tumor with minimal background fluorescence but also effectively discriminate between
glioblastoma and inflammatory tissues for the first time, leading to detection of
glioblastoma in vivo with high target-to-background ratios and minimal background fluorescence. Therefore, hydro-Cy5-RWrNR is the first
integrin αvβ3-specific hydrocyanine probe and has great potential in precise
tumor diagnosis because of its cooperative targeting of
integrin αvβ3 and ROS.