Breast cancer is very heterogeneous and the most frequently
diagnosed
cancer worldwide, and precise therapy targeting specific subtypes
may improve the survival rates of breast cancer patients. In this
study, we designed a biomimetic vesicle by camouflaging catalytic
DNA machinery with a breast cancer cell membrane, which enabled the
molecular classification of circulating exosomes for subtype-based
diagnosis through homotypic recognition. In addition, the vesicles
specifically targeted and fused with breast cancer exosomes with phenotypic
homology and manipulated the DNA machinery to amplify electrochemical
signaling using exosomal RNA as an endogenous trigger. The biomimetic
vesicles prepared with MCF-7 cancer cell-derived membranes were shown
to recognize estrogen receptor-positive breast cancer exosomes and
exhibited a low detection limit of 557 particles mL–1 with microRNA-375 used as the endogenous biomarker. Furthermore,
the biomimetic vesicles prepared with MDA-MB-231 cancer cell-derived
membranes displayed satisfactory performance in a homotypic analysis
of triple-negative breast cancer exosomes with a potential therapeutic
target, PD-L1 mRNA, used as the endogenous biomarker. Most importantly,
cross-validation experiments confirmed the high accuracy and selectivity
of this homotypic recognition-driven analysis for molecular subtyping
of breast cancer. When applied to clinical samples of breast cancer
patients, the vesicles demonstrated feasibility and reliability for
evaluating the molecular features of cancer cell-derived exosomes
and enabled stage-specific monitoring of breast cancer patients because
the electrochemical signals showed a positive correlation with disease
progression. Therefore, this work may provide new ideas for the precise
diagnosis and personalized treatment of breast cancer patients throughout
the whole disease process.
Micro/nanocarriers hold great potential in bioanalysis for molecular recognition and signal amplification but are frequently hampered by harsh synthesis conditions and timeconsuming labeling processes. Herein, we demonstrate that Escherichia coli (Ec) can be engineered as an efficient biocarrier for electrochemical immunoassay, which can load ultrahigh amounts of redox indicators and simultaneously be decorated with detection antibodies via a facile polydopamine (PDA)mediated coating approach. Compared with conventional carrier materials, the entire preparation of the Ec biocarrier is simple, highly sustainable, and reproducible. Moreover, immune recognition and electrochemical transduction are performed independently, which eliminates the accumulation of biological interference on the electrode and simplifies electrode fabrication. Using human epidermal growth factor receptor 2 (HER2) as the model target, the proposed immunosensor exhibits excellent analytical performance with a low detection limit of 35 pg/mL. The successful design and deployment of Ec biocarrier may provide new guidance for developing biohybrids in biosensing applications.
Covalent organic frameworks (COFs) are gaining growing interest owing to their various structures and versatility. Since their specific physical–chemical characteristics endow them great usage potentiality in biosensing, we herein have synthesized spherical COFs with regular shape and good dispersion, which are further used for the design of a novel nanoprobe by modifying Histostar on the surface of the COFs. Moreover, we have applied a nanoprobe for the fabrication of an electrochemical biosensor to detect exosomes. Since Histostar is a special polymer, conjugated with many secondary antibodies (IgG), and HRP can increase the availability of HRP at the antigenic site, the biosensor can have a strong signal amplification ability. Meanwhile, since COFs with high porosity can be loaded with a huge amount of Histostar, the sensitivity of the biosensor can be further improved. With such a design, the proposed biosensor can achieve a low exosomes detection limit of 318 particles/µL, and a wide linear detection range from 103 particles/µL to 108 particles/µL. So, this work may offer a promising platform for the ultrasensitive detection of exosomes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.