2. Academic Validation
  3. Metal-ion-chelating phenylalanine nanostructures reverse immune dysfunction and sensitize breast tumour to immune checkpoint blockade

Metal-ion-chelating phenylalanine nanostructures reverse immune dysfunction and sensitize breast tumour to immune checkpoint blockade

  • Nat Nanotechnol. 2024 Aug 26. doi: 10.1038/s41565-024-01758-3.
Mixiao Tan # 1 2,  Guoliang Cao # 1 3,  Rupeng Wang 3,  Long Cheng 2,  Wenping Huang 1,  Yue Yin 1,  Haixia Ma 1,  Shih-Hsin Ho 3,  Zhigang Wang 2,  Motao Zhu 1,  Haitao Ran 4,  Guangjun Nie 5 6,  Hai Wang 7 8
Affiliations

Affiliations

  • 1 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People's Republic of China.
  • 2 The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, People's Republic of China.
  • 3 State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, People's Republic of China.
  • 4 The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, People's Republic of China. ranhaitao@cqmu.edu.cn.
  • 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People's Republic of China. niegj@nanoctr.cn.
  • 6 University of Chinese Academy of Sciences, Beijing, People's Republic of China. niegj@nanoctr.cn.
  • 7 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, People's Republic of China. wanghai@nanoctr.cn.
  • 8 University of Chinese Academy of Sciences, Beijing, People's Republic of China. wanghai@nanoctr.cn.
  • # Contributed equally.
PMID: 39187583 DOI: 10.1038/s41565-024-01758-3
Abstract

An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving Immune Checkpoint blockade-based Cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating L-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating L-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated Cancer Immunotherapy.

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