Amphiphilic hemicyanine molecular probes crossing the blood-brain barrier for intracranial optical imaging of glioblastoma

Intracranial optical imaging of glioblastoma (GBM) is challenging due to the scarcity of effective probes with blood-brain barrier (BBB) permeability and sufficient imaging depth. Herein, we describe a rational strategy for designing optical probes crossing the BBB based on an electron donor-π-acceptor system to adjust the lipid/water partition coefficient and molecular weight of probes. The amphiphilic hemicyanine dye (namely, IVTPO), which exhibits remarkable optical properties and effective BBB permeability, is chosen as an efficient fluorescence/photoacoustic probe for in vivo real-time imaging of orthotopic GBM with high resolution through the intact skull. Abnormal leakage of IVTPO adjacent to the developing tumor is unambiguously observed at an early stage of tumor development prior to impairment of BBB integrity, as assessed by commercial Evans blue (EB). Compared with EB, IVTPO demonstrates enhanced optical imaging capability and improved tumor-targeting efficacy. These results offer encouraging insights into medical diagnosis of intracranial GBM.