Journal
BIOSENSORS & BIOELECTRONICS
Volume 168, Issue -, Pages -Publisher
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2020.112520
Keywords
Aptamer; Exosome; Protein profiling; AIEgen; Liquid biopsy
Categories
Funding
- National Natural Science Foundation of China [81702100, 81902165]
- Major Program of Health Care and Innovation of Guangzhou Project [201704020213, 201604020015]
- Natural Science Foundation of Guangdong Province [2019A1515011077]
- Basic and Applied Basic Research Programs of Guangdong Province [2019B1515120074]
- College Students' Innovative Entrepreneurial Training Plan Program of Southern Medical University [201812121272]
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Surface protein patterns of tumor-derived exosomes could be promising noninvasive diagnostic biomarkers for liquid biopsy. However, a convenient and cost-effective platform for exosomal protein profiling is still lacking. Herein, a facile fluorescent aptasensor is developed to assess exosomal tumor-associated proteins, combining aptamers, aggregation-induced emission luminogens (AlEgens), and graphene oxide (GO) as recognition elements, fluorescent dye, and the quencher, respectively. Specifically, numberous TPE-TAs could bind one aptamer and form aggregates rapidly, resulting in an amplified fluorescence signal. In the absence of tumor-derived exosomes, GO absorbs the TPE-TAs/aptamer complex, allowing fluorescence quenching. When the target exosomes are introduced, the aptamer preferentially binds with its target. Thus the TPE-TAs/aptamer complexes detach from GO surface, followed by the appearance of a turn-on fluorescent signal. Under the optimized conditions, the linear range of target exosomes is estimated to be 4.07 x 10(5) to 1.83 x 10(7) particles/mu L (0.68-30.4 pM) with a detection limit of 3.43 x 10(5) particles/mu L (0.57 pM). This strategy demonstrated great performance in differentiating prostate cancer from healthy individuals (AUC: 0.9790). Furthermore, by profiling three tumor-associated protein markers including epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), and human epidermal growth factor receptor 2 (HER2) on exosomes in a breast tumor cohort, this sensing platform diagnoses breast tumors with high efficiency (AUC: 0.9845) and exhibits a high sensitivity of 97.37% for distinguishing malignant breast cancers, where the stage I cases were detected with 92.31% sensitivity. Therefore, this aptasensor provides a promising strategy to profile tumor-derived exosomal proteins for early diagnosis in liquid biopsy.
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