ConspectusDNA performs a vital function as a carrier of genetic code, but in the field of nanotechnology, DNA molecules can catalyze chemical reactions in the cell, that is, DNAzymes, or bind with target-specific ligands, that is, aptamers. These functional DNAs with different modifications have been developed for sensing, imaging, and therapeutic systems. Thus, functional DNAs hold great promise for future applications in nanotechnology and bioanalysis. However, these functional DNAs face challenges, especially in the field of biomedicine. For example, functional DNAs typically require the use of cationic transfection reagents to realize cellular uptake. Such reagents enter the cells, increasing the difficulty of performing bioassays in vivo and potentially damaging the cell’s nucleus. To address this obstacle, nanomaterials, such as metallic, carbon, silica, or magnetic materials, have been utilized as DNA carriers or assistants. In this Account, we describe selected examples of functional DNA-containing nanomaterials and their applications from our recent research and those of others. As models, we have chosen to highlight DNA/nanomaterial complexes consisting of gold nanoparticles, graphene oxides, and aptamer–micelles, and we illustrate the potential of such complexes in biosensing, imaging, and medical diagnostics.Under proper conditions, multiple ligand–receptor interactions, decreased steric hindrance, and increased surface roughness can be achieved from a high density of DNA that is bound to the surface of nanomaterials, resulting in a higher affinity for complementary DNA and other targets. In addition, this high density of DNA causes a high local salt concentration and negative charge density, which can prevent DNA degradation. For example, DNAzymes assembled on gold nanoparticles can effectively catalyze chemical reactions even in living cells. And it has been confirmed that DNA–nanomaterial complexes can enter cells more easily than free single-stranded DNA.Nanomaterials can be designed and synthesized in needed sizes and shapes, and they possess unique chemical and physical properties, which make them useful as DNA carriers or assistants, excellent signal reporters, transducers, and amplifiers. When nanomaterials are combined with functional DNAs to create novel assay platforms, highly sensitive biosensing and high-resolution imaging result. For example, gold nanoparticles and graphene oxides can quench fluorescence efficiently to achieve low background and effectively increase the signal-to-background ratio. Meanwhile, gold nanoparticles themselves can be colorimetric reporters because of their different optical absorptions between monodispersion and aggregation.DNA self-assembled nanomaterials contain several properties of both DNA and nanomaterials. Compared with DNA–nanomaterial complexes, DNA self-assembled nanomaterials more closely resemble living beings, and therefore they have lower cytotoxicity at high concentrations. Functional DNA self-assemblies also have high density of DNA for multiva...
The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53, conferring tumor development and survival. Antagonists targeting the p53-binding domains of MDM2 and MDMX kill tumor cells both in vitro and in vivo by reactivating the p53 pathway, promising a class of antitumor agents for cancer therapy. Aided by native chemical ligation and mirror image phage display, we recently identified a D-peptide inhibitor of the p53-MDM2 interaction termed The tumor suppressor protein p53 is a transcription factor that transactivates, in response to cellular stresses, the expression of various target genes that mediate cell cycle arrest, senescence, or apoptosis (1). Dubbed the "guardian of the genome" (2), p53 is critical for maintaining genetic stability and preventing tumor development (3). Not surprisingly, loss of p53 activity resulting from point mutations in the TP53 gene is responsible for approximately 50% of human tumors. Although p53 retains WT status in many other tumors, its tumor suppressor activity and in vivo stability are abrogated by regulatory molecules such as the E3 ubiquitin ligase MDM2 and its homologue MDMX (4, 5). Amplified or over-expressed in a significant fraction of cancers without concomitant TP53 mutation, MDM2 and MDMX directly contribute to p53 inactivation and tumor survival.MDM2 itself is transcriptionally inducible by p53 in a negative feedback loop (6). MDM2 binds the N-terminal transactivation domain of p53 with high affinity to block p53 regulating responsive gene expression (7). More importantly, MDM2 controls p53 stability by targeting the tumor suppressor protein for ubiquitinmediated constitutive degradation (8-10). Although MDMX lacks E3 ubiquitin ligase activity, the MDM2 homologue acts as an effective transcriptional antagonist of p53, and nonredundantly impedes p53-induced growth inhibitory and apoptotic responses (4, 5). In addition, MDMX forms heterodimers with MDM2 through their C-terminal RING finger domains, stimulating MDM2-mediated ubiquitination and degradation of p53 and MDMX itself (11-13). The interplay between MDM2 and MDMX confers a robust p53 inactivation in tumorigenesis (14).Recent studies show that restoring endogenous p53 activity can halt the growth of cancerous tumors in mice through cell typedependent multiple mechanisms, including apoptosis, senescence, and senescence-triggered innate inflammatory responses (15-17). Thus, antagonists of MDM2 and MDMX that activate the p53 pathway can potentially be developed into a class of therapeutic agents for cancer treatment (14). Much of the current efforts have been focused on combinatorial library search for and structurebased rational design of low molecular weight antagonists of MDM2 (18). Successful examples include a cis-imidazoline analogue, termed nutlin-3, and, a spiro-oxindole-derived compound, termed 20). For optimal efficacy, however, dual specific inhibitors may be needed to target both MDM2 and MDMX (14).We previously reported the synthesis of the p53...
DNAzymes, screened through in vitro selection, have shown great promise as molecular tools in the design of biosensors and nanodevices. The catalytic activities of DNAzymes depend specifically on cofactors and show multiple enzymatic turnover properties, which make DNAzymes both versatile recognition elements and outstanding signal amplifiers. Combining nanomaterials with unique optical, magnetic and electronic properties, DNAzymes may yield novel fluorescent, colorimetric, surface-enhanced Raman scattering (SERS), electrochemical and chemiluminescent biosensors. Moreover, some DNAzymes have been utilized as functional components to perform arithmetic operations or as "walkers" to move along DNA tracks. DNAzymes can also function as promising therapeutics, when designed to complement target mRNAs or viral RNAs, and consequently lead to down-regulation of protein expression. This feature article focuses on the most significant achievements in using DNAzymes as recognition elements and signal amplifiers for biosensors, and highlights the applications of DNAzymes in logic gates, DNA walkers and nanotherapeutics.
In contrast to one-photon microscopy, two-photon probe-based fluorescent imaging can provide improved three-dimensional spatial localization and increased imaging depth. Consequently, it has become one of the most attractive techniques for studying biological events in living cells and tissues. However, the quantitation of these probes is primarily based on single-emission intensity change, which tends to be affected by a variety of environmental factors. Ratiometric probes, on the other hand, can eliminate these interferences by the built-in correction of the dual emission bands, resulting in a more favorable system for imaging living cells and tissues. Herein, for the first time, we adopted a through-bond energy transfer (TBET) strategy to design and synthesize a small molecular ratiometric two-photon fluorescent probe for imaging living cells and tissues in real time. Specifically, a two-photon fluorophore (D-π-A-structured naphthalene derivative) and a rhodamine B fluorophore are directly connected by electronically conjugated bond to form a TBET probe, or Np-Rh, which shows a target-modulated ratiometric two-photon fluorescence response with highly efficient energy transfer (93.7%) and two well-resolved emission peaks separated by 100 nm. This novel probe was then applied for two-photon imaging of living cells and tissues and showed high ratiometric imaging resolution and deep-tissue imaging depth of 180 μm, thus demonstrating its practical application in biological systems.
We describe a comprehensive protocol for the preparation of multifunctional DNA nanostructures termed nanoflowers (NFs), which are self-assembled from long DNA building blocks generated via rolling-circle replication (RCR) of a designed template. NF assembly is driven by liquid crystallization and dense packaging of building blocks, which eliminates the need for conventional Watson-Crick base pairing. As a result of dense DNA packaging, NFs are resistant to nuclease degradation, denaturation or dissociation at extremely low concentrations. By manually changing the template sequence, many different functional moieties including aptamers, bioimaging agents and drug-loading sites could be easily integrated into NF particles, making NFs ideal candidates for a variety of applications in biomedicine. In this protocol, the preparation of multifunctional DNA NFs with highly tunable sizes is described for applications in cell targeting, intracellular imaging and drug delivery. Preparation and characterization of functional DNA NFs takes ~5 d; the following biomedical applications take ~10 d.
Functional nucleic acid (FNA)-based sensing systems have been developed for efficient detection of a wide range of biorelated analytes by employing DNAzymes or aptamers as recognition units. However, their intracellular delivery has always been a concern, mainly in delivery efficiency, kinetics, and the amount of delivered FNAs. Here we report a DNA dendrimer scaffold as an efficient nanocarrier to deliver FNAs and to conduct in situ monitoring of biological molecules in living cells. A histidine-dependent DNAzyme and an anti-ATP aptamer were chosen separately as the model FNAs to make the FNA dendrimer. The FNA-embedded DNA dendrimers maintained the catalytic activity of the DNAzyme or the aptamer recognition function toward ATP in the cellular environment, with no change in sensitivity or specificity. Moreover, these DNA dendrimeric nanocarriers show excellent biocompatibility, high intracellular delivery efficiency, and sufficient stability in a cellular environment. This FNA dendrimeric nanocarrier may find a broad spectrum of applications in biomedical diagnosis and therapy.
Rapid progress achieved on perovskite solar cells raises the expectation for their further development toward practical applications. Moisture sensitivity of perovskite materials is one of the major obstacles which limits the long-term durability of the perovskite solar cells, especially in outdoor operation where rainfall and water accumulation on the solar panels often occur. Micro/nanopinholes within the functional layers of the devices usually lead to water vapor penetration, thus subsequent decomposition of perovskites, and finally poor device performance and shortened operational lifetime. In this work, low-temperature atomic layer deposition (ALD) technique was utilized to incorporate pinhole-free metal oxide layers (TiO and AlO) into an inverted perovskite solar cell consisting of indium tin oxide/NiO/perovskite/PCBM/TiO/Ag. The interface properties between the inserted TiO layer and the perovskite layer were investigated by X-ray photoelectron spectroscopy. The results showed that TiO ALD fabrication process had made negligible degradation to the perovskite layer. The TiO layer can significantly reduce interfacial charge recombination loss, improve interfacial contact, and enhance water resistance. A maximum power conversion efficiency (PCE) of 18.3% was achieved for devices with TiO interface layers. A stacked AlO encapsulation layer was designed and deposited on top of the devices to further improve device stability under harsh environmental conditions. The encapsulated devices with the best performance retained 97% of the initial PCE after being stored in ambient condition for a thousand hours. They also showed great water resistance, and no significant degradation in terms of PCE and photocurrent of the devices was observed after they were immersed in deionized water for as long as 2 h. Our approach offers a promising way of developing highly efficient and stable perovskite solar cells under real-world operational conditions.
Solar cells based on organometal hybrid perovskites have exhibited promising commercialization potential owing to their high efficiency and low-cost manufacturing. However, the poor outdoor operational stability of perovskite solar cells restricted their practical application, and moisture permeation and organic compounds volatilization are realized as the main factors accelerating performance degradation. Herein, we developed a composite encapsulation, by sequentially depositing a compact Al 2 O 3 layer and a hydrophobic 1H,1H,2H,2H-perfluorodecyltrichlorosilane layer on the completed device, to efficiently circumvent vapor permeability. Thus, the stability of the encapsulated perovskite solar cells was systematically investigated under simulated operational conditions. It was found that the MAPbI 3 perovskite was prone to decay into solid PbI 2 and organic vapor at high temperature or upon light illumination, and the decomposition was reversible in a well-encapsulated environment, resulting in reversible performance degradation and recovery. The enhanced thermal stability was ascribed to the competition between the perovskite decomposition and reverse synthesis. The as-prepared high-quality, multilayered encapsulation scheme demonstrated superior sealing property, and no obvious performance decline was observed when the device was stored under ambient air, continuous light illumination, double 85 condition (85 °C, 85% humidity), or even water immersion. Therefore, this work paves the way for a scalable and robust encapsulation strategy feasible to hybrid perovskite optoelectronics in a reproducible manner.
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.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.