2. Academic Validation
  3. Bioengineered hybrid dual-targeting nanoparticles reprogram the tumour microenvironment for deep glioblastoma photodynamic therapy

Bioengineered hybrid dual-targeting nanoparticles reprogram the tumour microenvironment for deep glioblastoma photodynamic therapy

  • Nat Commun. 2025 Aug 18;16(1):7672. doi: 10.1038/s41467-025-63081-2.
Rongrong Zhao # 1 2,  Ying Hou # 3,  Boyan Li # 1 2,  Ziwen Pan # 1 2,  Jiawei Qiu 1 2,  Qingtong Wang 1 2,  Yanhua Qi 1 2,  Zhe Han 1 2,  Hongyu Zhao 1 2,  Hong Liu 4 5,  Weijia Zhou 6,  Gang Li 7 8,  Hao Xue 9 10
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China.
  • 2 Shandong Key Laboratory of Brain Health and Function Remodelling, Jinan, 250012, China.
  • 3 Institute for Advanced Interdisciplinary Research (iAIR), School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China.
  • 4 Institute for Advanced Interdisciplinary Research (iAIR), School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China. hongliu@sdu.edu.cn.
  • 5 State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, China. hongliu@sdu.edu.cn.
  • 6 Institute for Advanced Interdisciplinary Research (iAIR), School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, China. ifc_zhouwj@ujn.edu.cn.
  • 7 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China. dr.ligang@sdu.edu.cn.
  • 8 Shandong Key Laboratory of Brain Health and Function Remodelling, Jinan, 250012, China. dr.ligang@sdu.edu.cn.
  • 9 Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, 250012, China. xuehao@sdu.edu.cn.
  • 10 Shandong Key Laboratory of Brain Health and Function Remodelling, Jinan, 250012, China. xuehao@sdu.edu.cn.
  • # Contributed equally.
PMID: 40826003 DOI: 10.1038/s41467-025-63081-2
Abstract

Glioblastoma (GBM) poses significant therapeutic challenges due to its hypoxic and immunosuppressive tumour microenvironment (TME), low immunogenicity and physical barriers. While combining photodynamic therapy (PDT) with immunotherapy holds promise, its efficacy is hampered by insufficient immune activation. In this study, we develop a multifunctional photodynamic-enhanced biomimetic intelligent nanoplatform (FBFO@HM@aOPN) responsive to the TME. The nanoplatform consists of a dual-enzyme nanozyme encapsulated in a prokaryotic-eukaryotic hybrid membrane, further modified with a pH-sensitive tumor-targeting antibody. After systemic administration, FBFO@HM@aOPN selectively accumulates in the GBM through vascular regulation and extracellular matrix (ECM) remodelling while generating oxygen to alleviate hypoxia. Crucially, the platform concurrently induces immunogenic death in tumour cells and reprograms protumoral macrophages to antitumor phenotypes. This dual action robustly activates both innate and adaptive immunity, significantly inhibiting GBM growth. Furthermore, when combined with anti-PD1 immunotherapy, the nanoplatform dramatically boosts the treatment effect and effectively prevents postsurgical tumour recurrence. Therefore, our work offers a multimodal platform for stimulating anti-tumour immunity, with potential applicability for GBM patients.

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