In Situ Programmable DNA Circuit-Promoted Electrochemical Characterization of Stemlike Phenotype in Breast Cancer

Cao, Ya; Yu, Xiaomeng; Han, Bing; Dong, Lijuan; Xu, Jingjing; Dai, Yuhao; Li, Genxi; Zhao, Jing

doi:10.1021/jacs.1c06436

Cited by 37 publications

(26 citation statements)

References 42 publications

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“…Many new methods have been revealed, such as the use of DNA circuits in microenvironment regulation, [ 136 ] immunotherapy, [ 137 ] and cancer stem cell diagnosis. [ 138 ] Driven by various advanced functional materials, DNA logic circuit will play a more important role in the field of intelligent disease diagnosis and treatment.…”

Section: Discussionmentioning

confidence: 99%

DNA Logic Circuits for Cancer Theranostics

Chen

Zhang

et al. 2022

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solutions for precise cancer theranostics based on tumor microenvironment (TME) and biomarkers. [3][4][5][6][7] Nano-drugs such as liposomes, [8] polymer nanoparticles, [9] and inorganic nanoparticles [10] have been approved by Food and Drug Administration for the clinical treatment of cancer. However, current nanomedicine technologies lack intelligence which is the capability of autonomous computing in biological samples. Owing to the basepairing language and dynamic assembly of DNA strands, DNA-based logic devices/ circuits hold great potential to enhance the intelligence of nanomedicine.DNA nanotechnology began with the DNA four-arm junction structure proposed by Seeman in the 1980s. [11] On the basis of the Watson-Crick base pairing principle, such nanotechnology creates a variety of controllable nanoscale structures based on self-assembly of nucleic acid, and then built up static DNA nano structures such as DNA tiles and DNA origami by bottom-up approach. [12] The development of static DNA nanotechnology creates highly stable and variable DNA nanostructures showing the applications in nanomedicine including molecular imaging, drug delivery, biosensors, and the revolution of data storage. [13][14][15][16][17][18] Because nucleic acid materials have excellent structural controllability, biosafety, and functional diversity, they have emerged as excellent materials for the early diagnosis and timely treatment of cancer. [19] DNA nanotechnology had been further developed by Yurke et al. They constructed the first DNA molecular machine and proposed the concept of toehold-mediated strand displacement (TMSD) for the first time, [20] which opened a new era of dynamic DNA nanotechnology. Dynamic DNA nanotechnology utilizes a nonequilibrium nucleic acid system based on TMSD [21] or enzymatic reactions, to develop DNA nanomechanical devices, [22] and molecular logic networks. [23][24][25][26][27][28] Through the cascade and integration of multiple DNA reaction modules, DNA logic circuit is developed for cancer theranostics. [29,30] The basic DNA logic circuit can be conceptualized as a black box, which accepts the DNA strand as input and implements signal conversion by performing modular circuit elements such as TMSD and enzymatic reaction, [31] finally releases the DNA strand as output. [32] In cancer theranostics, DNA logic circuits can respond to the microenvironment or specific biomarkers of tumor, through signal transduction, logical judgment, signal amplification, Cancer diagnosis and therapeutics (theranostics) based on the tumor microenvironment (TME) and biomarkers has been an emerging approach for precision medicine. DNA nanotechnology dynamically controls the self-assembly of DNA molecules at the nanometer scale to construct intelligent DNA chemical reaction systems. The DNA logic circuit is a particularly emerging approach for computing within the DNA chemical systems. DNA logic circuits can sensitively respond to tumor-specific markers and the TME through logic operations and signal amplification, to genera...

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Section: Discussionmentioning

confidence: 99%

DNA Logic Circuits for Cancer Theranostics

Chen

Zhang

et al. 2022

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“…31 Then, this structure is immobilized onto anti-CD44-functionalized immune-magnetic beads (anti-CD44@ IMBs) through its immune interaction with surface-expressed CD44, which is usually overexpressed in BC. 32 The cancer CMVs are designed to specifically adhere to BC exosomes derived from the same cell source and are integrated with these exosomes through homotypic fusion. Exosomal RNA shows better stability than blood RNA and may provide varied information related to tumor characteristics.…”

Section: ■ Introductionmentioning

confidence: 99%

Molecular Characterization of Exosomes for Subtype-Based Diagnosis of Breast Cancer

Cao

Zeng

et al. 2022

J. Am. Chem. Soc.

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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.

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“…The output signal higher or lower than a threshold was defined as 1 and 0, respectively . Different input combinations will result in different outputs according to the truth table permutation . Recently, some excellent logic gates were fabricated on the basis of molecular computations, such as AND, OR, XOR, NAND, half adder, half subtractor, etc. − Most of the previously reported logic gates employed nucleic acids, , proteins, , and heavy metal ions , as inputs.…”

Section: Introductionmentioning

confidence: 99%

“…A total of 200 nM DNA (3 and 4) was then added and incubated for 50 min at room temperature. The mixture was incubated with 200 nM crRNA, 50 nM Cas12a, and 200 nM DNA (5) for 90 min at room temperature. Fluorescence signals were obtained on SpectraMax i3x (Molecular Devices, San Jose, CA, U.S.A.), with the excitation wavelength set at 490 nm and emission wavelength recorded at 525 nm.…”

Section: ■ Introductionmentioning

confidence: 99%

Fluorescent Detection of Two Pesticides Based on CRISPR-Cas12a and Its Application for the Construction of Four Molecular Logic Gates

Yan

Shi

Chen

2022

J. Agric. Food Chem.

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An intelligent detection platform was developed through molecular logic gate operation based on CRISPR-Cas12a and signal amplification circuits using two kinds of pesticides [acetamiprid (ACE) and atrazine (ATR)] as inputs. The pesticide–aptamer bindings activate the signal amplification process to produce numerous double-stranded DNA, which can be identified by CRISPR-Cas12a. Under the optimal assay conditions, the sensor exhibits excellent analytical performance, with the detection limits for ACE and ATR of 2.5 and 0.2 pM, respectively. The practicality of the platform was verified by testing pesticide concentrations in food samples. Several molecular logic gates (OR, AND, XOR, and INHIBIT) were constructed using “0” and “1” to encode the target pesticides and the fluorescence readout. The logic detection platform with simple operation, high sensitivity, and multiple logic functions is promising to become a powerful sensing system for the intelligent assay of different pesticides in food samples.

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In Situ Programmable DNA Circuit-Promoted Electrochemical Characterization of Stemlike Phenotype in Breast Cancer

Cited by 37 publications

References 42 publications

DNA Logic Circuits for Cancer Theranostics

DNA Logic Circuits for Cancer Theranostics

Molecular Characterization of Exosomes for Subtype-Based Diagnosis of Breast Cancer

Fluorescent Detection of Two Pesticides Based on CRISPR-Cas12a and Its Application for the Construction of Four Molecular Logic Gates

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