DNA Supramolecular Assembly on Micro/Nanointerfaces for Bioanalysis

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS: Facing increasing demand for precision medicine, materials chemistry systems for bioanalysis with accurate molecular design, controllable structure, and adjustable biological activity are required. As a genetic biomacromolecule, deoxyribonucleic acid (DNA) is created via precise, efficient, and mild processes in life systems and can in turn precisely regulate life activities. From the perspective of materials chemistry, DNA possesses the characteristics of sequence programmability and can be endowed with customized functions by the rational design of sequences. In recent years, DNA has been considered to be a potential biomaterial for analysis and has been applied in the fields of bioseparation, biosensing, and detection imaging. To further improve the precision of bioanalysis, the supramolecular assembly of DNA on micro/nanointerfaces is an effective strategy to concentrate functional DNA modules, and thus the functions of DNA molecules for bioanalysis can be enriched and enhanced. Moreover, the new modes of DNA supramolecular assembly on micro/nanointerfaces enable the integration of DNA with the introduced components, breaking the restriction of limited functions of DNA materials and achieving more precise regulation and manipulation in bioanalysis. In this Account, we summarize our recent work on DNA supramolecular assembly on micro/nanointerfaces for bioanalysis from two main aspects. In the first part, we describe DNA supramolecular assembly on the interfaces of microscale living cells. The synthesis strategy of DNA is based on rolling-circle amplification (RCA), which generates ultralong DNA strands according to circular DNA templates. The templates can be designed with complementary sequences of functional modules such as aptamers, which allow DNA to specifically bind with cellular interfaces and achieve efficient cell separation. In the second part, we describe DNA supramolecular assembly on the interfaces of nanoscale particles. DNA sequences are designed with functional modules such as targeting, drug loading, and gene expression and then are assembled on interfaces of particles including upconversion nanoparticles (UCNPs), gold nanoparticles (AuNPs), and magnetic nanoparticle (MNPs). The integration of DNA with these functional particles achieves cell manipulation, targeted tumor imaging, and cellular regulation. The processes of interfacial assembly are well controlled, and the functions of the obtained bioanalytical materials can be flexibly regulated. We envision that the work on DNA supramolecular assembly on micro/nanointerfaces will be a typical paradigm for the construction of more bioanalytical materials, which we hope will facilitate the development of precision medicine.

Nanopore-Based Fingerprint Immunoassay Based on Rolling Circle Amplification and DNA Fragmentation

“…In this scheme, we combine isothermal nucleic acid amplification and a sandwich ELISA immunocomplex, , with controlled sequence-specific cleavage to enhance the sensitivity of nanopores. Rolling circle amplification (RCA) with the highly processive enzyme phi29 polymerase generates ultralong ssDNA (∼100 knt), an ideal product for signal amplification. − We employ this isothermal amplification method that is rapid, cost-effective, easy-to-use, and more tolerant to inhibitory components from crude samples than polymerase chain reaction (PCR), another enzyme-based amplification method . Restriction enzyme-based digestion of the RCA product generates many DNA fragments of different sizes and structures, which are detected using an α-hemolysin nanopore (Figure A).…”

Erythrocyte membrane-camouflaged DNA-functionalized upconversion nanoparticles for tumor-targeted chemotherapy and immunotherapy

“…21 According to research, UCNPs that carry and protect single-stranded DNA have been employed in cancer treatment and bioimaging. 22 On the one hand, the fast coordination of the phosphate groups on the DNA backbone with Ln 3+ exposed on the UCNPs causes DNA absorption onto the UCNP surface. 23 This method does not require chemical modification of oligonucleotides and is time-saving and highly efficient.…”

Cascade dynamic assembly/disassembly of DNA nanoframework enabling the controlled delivery of CRISPR-Cas9 system

“…In recent decades, DNA nanomaterials have been developed as promising carriers for drug delivery (23)(24)(25)(26). The unique properties of DNA nanomaterials are conducive to increasing blood circulation (27,28), promoting tissue penetration (29,30), and accelerating cellular uptake (31,32). In particular, the dynamic assembly/disassembly of DNA molecules via base pairing (33,34), and in response to pH (35,36), enzymes (37,38), and metal ions (39,40), facilitates the high-capability loading, precise targeting, and responsive release of drugs (41)(42)(43).…”