Near-infrared II fluorescence-guided glioblastoma surgery targeting monocarboxylate transporter 4 combined with photothermal therapyResearch in context
Hongyang Zhao,
Chunzhao Li,
Xiaojing Shi,
Jinnan Zhang,
Xiaohua Jia,
Zhenhua Hu,
Yufei Gao,
Jie Tian
Affiliations
Hongyang Zhao
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China; CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; Jilin Province Neuro-oncology Engineering Laboratory, Changchun, China; Jilin Provincial Key Laboratory of Neuro-oncology, Changchun, China
Chunzhao Li
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China
Xiaojing Shi
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
Jinnan Zhang
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China; Jilin Province Neuro-oncology Engineering Laboratory, Changchun, China; Jilin Provincial Key Laboratory of Neuro-oncology, Changchun, China
Xiaohua Jia
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Zhenhua Hu
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China; National Key Laboratory of Kidney Diseases, Beijing, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Yufei Gao
Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, Changchun, China; Jilin Province Neuro-oncology Engineering Laboratory, Changchun, China; Jilin Provincial Key Laboratory of Neuro-oncology, Changchun, China; Corresponding author. Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, No. 126 Xiantai Street, Changchun, 130033, China.
Jie Tian
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, China; School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China; National Key Laboratory of Kidney Diseases, Beijing, China; Beijing Advanced Innovation Center for Big Data-based Precision Medicine, School of Engineering Medicine, Beihang University, Beijing, China; Corresponding author. CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing, 100190, China.
Summary: Background: Surgery is crucial for glioma treatment, but achieving complete tumour removal remains challenging. We evaluated the effectiveness of a probe targeting monocarboxylate transporter 4 (MCT4) in recognising gliomas, and of near-infrared window II (NIR-II) fluorescent molecular imaging and photothermal therapy as treatment strategies. Methods: We combined an MCT4-specific monoclonal antibody with indocyanine green to create the probe. An orthotopic mouse model and a transwell model were used to evaluate its ability to guide tumour resection using NIR-II fluorescence and to penetrate the blood–brain barrier (BBB), respectively. A subcutaneous tumour model was established to confirm photothermal therapy efficacy. Probe specificity was assessed in brain tissue from mice and humans. Finally, probe effectiveness in photothermal therapy was investigated. Findings: MCT4 was differentially expressed in tumour and normal brain tissue. The designed probe exhibited precise tumour targeting. Tumour imaging was precise, with a signal-to-background (SBR) ratio of 2.8. Residual tumour cells were absent from brain tissue postoperatively (SBR: 6.3). The probe exhibited robust penetration of the BBB. Moreover, the probe increased the tumour temperature to 50 °C within 5 min of laser excitation. Photothermal therapy significantly reduced tumour volume and extended survival time in mice without damage to vital organs. Interpretation: These findings highlight the potential efficacy of our probe for fluorescence-guided surgery and therapeutic interventions. Funding: Jilin Province Department of Science and Technology (20200403079SF), Department of Finance (2021SCZ06) and Development and Reform Commission (20200601002JC); National Natural Science Foundation of China (92059207, 92359301, 62027901, 81930053, 81227901, U21A20386); and CAS Youth Interdisciplinary Team (JCTD-2021-08).
