Identifying tumor cell-released extracellular vesicles as biomarkers for breast cancer diagnosis by a three-dimensional hydrogel-based electrochemical immunosensor

J Nanobiotechnology. 2023 Dec 7;21(1):467. doi: 10.1186/s12951-023-02180-y.

Abstract

Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.

Keywords: Biomarker; Breast cancer; Early diagnosis; LC3+ extracellular vesicles; cancer subtypes and stages.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Biomarkers, Tumor / metabolism
  • Biosensing Techniques*
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / metabolism
  • Extracellular Vesicles* / metabolism
  • Female
  • Humans
  • Hydrogels
  • Immunoassay / methods
  • Mice

Substances

  • Hydrogels
  • Biomarkers, Tumor
  • Biomarkers