DNA Logic Circuits for Cancer Theranostics

Abstract

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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Advances and prospects of dynamic DNA nanostructures in biomedical applications

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An enzyme-powered microRNA discriminator for the subtype-specific diagnosis of breast cancer

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