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

in Science advances by Wei Qin, Honghui Li, Jiali Chen, Yang Qiu, Limin Ma, Liming Nie

TLDR

  • The study describes the development of IVTPO, a novel optical probe that crosses the blood-brain barrier for real-time imaging of glioblastoma tumors.
  • IVTPO demonstrates enhanced optical imaging capability and improved tumor-targeting efficacy compared to existing probes.
  • The study's findings offer promising insights into the early detection and diagnosis of intracranial glioblastoma.

Abstract

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.

Overview

  • The study focuses on developing an effective optical probe, IVTPO, to cross the blood-brain barrier (BBB) for real-time imaging of glioblastoma (GBM) tumors.
  • The probe is designed with an electron donor-π-acceptor system to adjust its lipid/water partition coefficient and molecular weight, allowing it to cross the BBB efficiently.
  • The study aims to investigate the potential of IVTPO as a fluorescence/photoacoustic probe for real-time imaging of orthotopic GBM with high resolution through the intact skull.

Comparative Analysis & Findings

  • IVTPO demonstrated remarkable optical properties and effective BBB permeability, allowing it to extravasate and accumulate in the tumor region.
  • Abnormal leakage of IVTPO adjacent to the developing tumor was observed at an early stage of tumor development, prior to impairment of BBB integrity.
  • IVTPO showed enhanced optical imaging capability and improved tumor-targeting efficacy compared to commercial Evans blue (EB) dye.

Implications and Future Directions

  • The study provides encouraging insights into the medical diagnosis of intracranial GBM, offering a potentially game-changing approach for early detection and treatment.
  • Future studies could explore the use of IVTPO as a probe for imaging other brain disorders or diseases that involve BBB disruption.
  • The rational design strategy employed in this study could be applied to develop optical probes for other biomedical applications, enabling real-time monitoring of disease progression and treatment efficacy.
Read Full Article