β-Ketoenamine covalent organic framework nanoplatform combined with immune checkpoint blockade via photodynamic immunotherapy inhibit glioblastoma progression

Tengfeng Yan; Qiuye Liao; Zhihao Chen; Yang Xu; Wenping Zhu; Ping Hu; Si Zhang; Yanze Wu; Lei Shu; Junzhe Liu; Min Luo; Hongxin Shu; Yilei Sheng; Li Wang; Chun Xu; Chang Lei; Hongming Wang; Qingsong Ye; Li Yang; Xingen Zhu

Bioactive Materials (Feb 2025)

β-Ketoenamine covalent organic framework nanoplatform combined with immune checkpoint blockade via photodynamic immunotherapy inhibit glioblastoma progression

Tengfeng Yan,
Qiuye Liao,
Zhihao Chen,
Yang Xu,
Wenping Zhu,
Ping Hu,
Si Zhang,
Yanze Wu,
Lei Shu,
Junzhe Liu,
Min Luo,
Hongxin Shu,
Yilei Sheng,
Li Wang,
Chun Xu,
Chang Lei,
Hongming Wang,
Qingsong Ye,
Li Yang,
Xingen Zhu

Affiliations

Tengfeng Yan: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China; Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, Jiangxi Province, 330000, China; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi Province, 330000, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Qiuye Liao: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Zhihao Chen: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Yang Xu: Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China
Wenping Zhu: JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi Province, 330000, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Ping Hu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Si Zhang: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Yanze Wu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Lei Shu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Junzhe Liu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Min Luo: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Hongxin Shu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Yilei Sheng: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China
Li Wang: College of Chemistry and Chemical Engineering, Jiangxi Normal University, 99 Ziyang Road, Nanchang, 330022, China
Chun Xu: Sydney Dental School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia; Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia
Chang Lei: Charles Perkins Centre, The University of Sydney, Camperdown, NSW, 2006, Australia; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia
Hongming Wang: College of Chemistry and Chemical Engineering and Jiangxi Provincial Key Laboratory of Functional Crystalline Materials Chemistry Nanchang University, Nanchang, 330031, China
Qingsong Ye: Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan University, 430060, Wuhan, China; Corresponding author. Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan University, 430060, Wuhan, China.
Li Yang: JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi Province, 330000, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, 330000, China; Corresponding author. Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, 330000, China.
Xingen Zhu: Department of Neurosurgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, 330000, China; Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, Jiangxi Province, 330000, China; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi Province, 330000, China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi Province, 330000, China; Corresponding author. The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province, 330000, China.

Journal volume & issue: Vol. 44
pp. 531 – 543

Abstract

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The synergistic approach of combining photodynamic immunotherapy with endogenous clearance of PD-L1 immune checkpoint blockade therapy holds promise for enhancing survival outcomes in glioblastoma (GBM) patients. The observed upregulation of O-GlcNAc glycolysis in tumors may contribute to the stabilization of endogenous PD-L1 protein, facilitating tumor immune evasion. This study presents a pH-adapted excited state intramolecular proton transfer (ESIPT)-isomerized β-ketoamide-based covalent organic framework (COF) nanoplatform (denoted as OT@COF-RVG). Temozolomide (TMZ) and OSMI-4 (O-GlcNAc transferase inhibitor) were integrated into COF cavities, then modified on the surface with polyethylene glycol and the rabies virus peptide RVG-29, showing potential for sensitizing TMZ chemotherapy and initiating photodynamic therapy (PDT). By inhibiting O-GlcNAc and promoting lysosomal degradation of PD-L1, OT@COF-RVG enhanced the effectiveness of immune checkpoint blockade (ICB) therapy. Additionally, treatment with OT@COF-RVG led to a notable elevation in reactive oxygen species (ROS) levels, thereby re-establishing an immunostimulatory state, inducing immunogenic cell death (ICD). In summary, our research unveiled a correlation between O-GlcNAc in GBM and the evasion of immune responses by tumors, while showcasing the potential of OT@COF-RVG in reshaping the immunosuppressive microenvironment of GBM and offering a more effective approach to immunotherapy in clinical settings.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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