Amphiphilic Hemicyanine Molecular Probes Crossing the Blood-brain Barrier for Intracranial Optical Imaging of Glioblastoma

Overview

Journal Sci Adv

Date 2025 Jan 15

PMID 39813352

Authors

Wei Qin

Honghui Li

Jiali Chen

Yang Qiu

Limin Ma

Liming Nie

Affiliations

Soon will be listed here.

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.

Citing Articles

Collagen fibers quantification for liver fibrosis assessment using linear dichroism photoacoustic microscopy.

Qiu Y, Li H, Yu K, Chen J, Qi L, Zhao Y Photoacoustics. 2025; 42:100694.

PMID: 39996157 PMC: 11849640. DOI: 10.1016/j.pacs.2025.100694.

References

Yao M, Li S, Wu X, Diao S, Zhang G, He H . Cellular origin of glioblastoma and its implication in precision therapy. Cell Mol Immunol. 2018; 15(8):737-739. PMC: 6141605. DOI: 10.1038/cmi.2017.159. View

Lim M, Xia Y, Bettegowda C, Weller M . Current state of immunotherapy for glioblastoma. Nat Rev Clin Oncol. 2018; 15(7):422-442. DOI: 10.1038/s41571-018-0003-5. View

Groothuis D, Vriesendorp F, Kupfer B, Warnke P, Lapin G, Kuruvilla A . Quantitative measurements of capillary transport in human brain tumors by computed tomography. Ann Neurol. 1991; 30(4):581-8. DOI: 10.1002/ana.410300411. View

Terstappen G, Meyer A, Bell R, Zhang W . Strategies for delivering therapeutics across the blood-brain barrier. Nat Rev Drug Discov. 2021; 20(5):362-383. DOI: 10.1038/s41573-021-00139-y. View

Hu Z, Fang C, Li B, Zhang Z, Cao C, Cai M . First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat Biomed Eng. 2019; 4(3):259-271. DOI: 10.1038/s41551-019-0494-0. View

Arvanitis C, Ferraro G, Jain R . The blood-brain barrier and blood-tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2019; 20(1):26-41. PMC: 8246629. DOI: 10.1038/s41568-019-0205-x. View

Hintersteiner M, Enz A, Frey P, Jaton A, Kinzy W, Kneuer R . In vivo detection of amyloid-beta deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol. 2005; 23(5):577-83. DOI: 10.1038/nbt1085. View

Wang Y, Wang X, Xie R, Burger J, Tong Y, Gong S . Overcoming the Blood-Brain Barrier for Gene Therapy via Systemic Administration of GSH-Responsive Silica Nanocapsules. Adv Mater. 2022; 35(6):e2208018. DOI: 10.1002/adma.202208018. View

Chen H, Liu L, Qian K, Liu H, Wang Z, Gao F . Bioinspired large Stokes shift small molecular dyes for biomedical fluorescence imaging. Sci Adv. 2022; 8(32):eabo3289. PMC: 9374339. DOI: 10.1126/sciadv.abo3289. View

10.

Zhu X, Huang Q, Jiang L, Nguyen V, Vu T, Devlin G . Longitudinal intravital imaging of mouse placenta. Sci Adv. 2024; 10(12):eadk1278. PMC: 10954206. DOI: 10.1126/sciadv.adk1278. View

11.

Wen P, Reardon D . Neuro-oncology in 2015: Progress in glioma diagnosis, classification and treatment. Nat Rev Neurol. 2016; 12(2):69-70. DOI: 10.1038/nrneurol.2015.242. View

12.

Zhang J, Yin X, Li C, Yin X, Xue Q, Ding L . A Multifunctional Photoacoustic/Fluorescence Dual-Mode-Imaging Gold-Based Theranostic Nanoformulation without External Laser Limitations. Adv Mater. 2022; 34(19):e2110690. DOI: 10.1002/adma.202110690. View

13.

Miao Y, Chen K, Chen C, Mi F, Lin Y, Chang Y . A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors. Adv Mater. 2021; 33(34):e2100701. DOI: 10.1002/adma.202100701. View

14.

Furtado D, Bjornmalm M, Ayton S, Bush A, Kempe K, Caruso F . Overcoming the Blood-Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases. Adv Mater. 2018; 30(46):e1801362. DOI: 10.1002/adma.201801362. View

15.

Fu W, Yan C, Guo Z, Zhang J, Zhang H, Tian H . Rational Design of Near-Infrared Aggregation-Induced-Emission-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultrasensitivity and High-Fidelity. J Am Chem Soc. 2019; 141(7):3171-3177. DOI: 10.1021/jacs.8b12820. View

16.

Lin L, Wang L . The emerging role of photoacoustic imaging in clinical oncology. Nat Rev Clin Oncol. 2022; 19(6):365-384. DOI: 10.1038/s41571-022-00615-3. View

17.

Zeng S, Liu X, Kafuti Y, Kim H, Wang J, Peng X . Fluorescent dyes based on rhodamine derivatives for bioimaging and therapeutics: recent progress, challenges, and prospects. Chem Soc Rev. 2023; 52(16):5607-5651. DOI: 10.1039/d2cs00799a. View

18.

Cai X, Bandla A, Mao D, Feng G, Qin W, Liao L . Biocompatible Red Fluorescent Organic Nanoparticles with Tunable Size and Aggregation-Induced Emission for Evaluation of Blood-Brain Barrier Damage. Adv Mater. 2016; 28(39):8760-8765. DOI: 10.1002/adma.201601191. View

19.

Wang S, Shi H, Wang L, Loredo A, Bachilo S, Wu W . Photostable Small-Molecule NIR-II Fluorescent Scaffolds that Cross the Blood-Brain Barrier for Noninvasive Brain Imaging. J Am Chem Soc. 2022; 144(51):23668-23676. PMC: 10010776. DOI: 10.1021/jacs.2c11223. View

20.

Wang X, Li P, Ding Q, Wu C, Zhang W, Tang B . Observation of Acetylcholinesterase in Stress-Induced Depression Phenotypes by Two-Photon Fluorescence Imaging in the Mouse Brain. J Am Chem Soc. 2019; 141(5):2061-2068. DOI: 10.1021/jacs.8b11414. View