2. Academic Validation
  3. Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer

Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer

  • ACS Nano. 2023 Jun 5. doi: 10.1021/acsnano.3c00350.
Min Wei 1 2 3 4,  Jingwen Bai 1 2 3 4 5,  Xiao Shen 1 2 3 4,  Kangliang Lou 1 2 3 4,  Yiyang Gao 1 2 3 4,  Ruichan Lv 6,  Peiyuan Wang 7,  Xiaolong Liu 7,  Guojun Zhang 1 2 3 5 8
Affiliations

Affiliations

  • 1 Cancer Center and Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
  • 2 Fujian Key Laboratory of Precision Diagnosis and Treatment in Breast Cancer, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
  • 3 Xiamen Key Laboratory of Endocrine-Related Cancer Precision Medicine, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
  • 4 Xiamen Research Center of Clinical Medicine in Breast and Thyroid Cancers, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
  • 5 Department of Oncology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
  • 6 Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710071, Shanxi, China.
  • 7 Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.
  • 8 Cancer Research Center of Xiamen University, School of Medicine, Xiamen University, Xiamen 361100, China.
PMID: 37272787 DOI: 10.1021/acsnano.3c00350
Abstract

Breast-conserving surgery (BCS) is the standard of care for early breast Cancer patients, while the high ratio of reoperation is still a challenge due to inaccurate margin assessments. In patients with locally advanced or advanced breast Cancer, radiotherapy is an important treatment for local control or improvement of quality of life. However, enhancing sensitization to radiotherapy is an unmet medical need. To solve the above clinical predicaments, a glutathione (GSH) exhausting virus-like silicon dioxide nanoprobe with Gd coating and folic acid (FA) modification is designed. After loading ICG in the mesopores, the VGd@ICG-FA probe efficiently targets tumor cells with high resolution, due to its virus-like morphology and folate acid anchoring. Especially, the fabricated nanoprobe enables the identification of tiny cancers and navigates precise surgery under NIR-II fluorescence imaging. Moreover, after the nanoprobes enter into the cytoplasm of Cancer cells, tetrasulfide linkages in the silica framework are broken under the triggering of high GSH concentrations. In turn, the broken framework exhausts GSH to disrupt intracellular Reactive Oxygen Species (ROS) homeostasis, and Gd produces more ROS under radiotherapy, further activating Ferroptosis, and resulting in the enhancement of radiotherapy in breast Cancer. Therefore, our nanoprobe exhibits tremendous potential as a NIR-II fluorescence imaging agent with no systematic side effects for precise Cancer surgery and nanotherapeutics for boosting radiation sensitivity in future clinical translation of breast Cancer.

Keywords

GSH-exhausting; NIR-II fluorescence imaging; breast cancer; imaging-guided surgery; radiation sensitization.

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