DNA nanostructures have shown potential in cancer therapy. However, their clinical application is hampered by the difficulty to deliver them into cancer cells and susceptibility to nuclease degradation. To overcome these limitations, we report herein a periodically ordered nick‐hidden DNA nanowire (NW) with high serum stability and active targeting functionality. The inner core is made of multiple connected DNA double helices, and the outer shell is composed of regularly arranged standing‐up hairpin aptamers. All termini of the components are hidden from nuclease attack, whereas the target‐binding sites are exposed to allow delivery to the cancer target. The DNA NW remained intact during incubation for 24 h in serum solution. Animal imaging and cell apoptosis showed that NWs loaded with an anticancer drug displayed long blood‐circulation time and high specificity in inducing cancer‐cell apoptosis, thus validating this approach for the targeted imaging and therapy of cancers.
Small interfering RNA (siRNA) is an effective therapeutic to regulate the expression of target genes in vitro and in vivo. Constructing a siRNA delivery system with high serum stability, especially responsive to endogenous stimuli, remains technically challenging. Herein we develop anti-degradation Y-shaped backbone-rigidified triangular DNA bricks with sticky ends (sticky-YTDBs) and tile them onto a siRNA-packaged gold nanoparticle in a programmed fashion, forming a multi-functional three-dimensional (3D) DNA shell. After aptamers are arranged on the exterior surface, a biocompatible siRNA-encapsulated core/shell nanoparticle, siRNA/Ap-CS, is achieved. SiRNAs are internally encapsulated in a 3D DNA shell and are thus protected from enzymatic degradation by the outermost layer of YTDB. The siRNAs can be released by endogenous miRNA and execute gene silencing within tumor cells, causing cell apoptosis higher than Lipo3000/siRNA formulation. In vivo treatment shows that tumor growth is completely (100%) inhibited, demonstrating unique opportunities for next-generation anticancer-drug carriers for targeted cancer therapies.
DNAzymes
with enzymatic activity identified from random DNA pools
by in vitro selection have recently attracted considerable
attention. In this work, a DNAzyme-based autonomous-motion (AM) molecular
machine is demonstrated for sensitive simultaneous imaging of different
intracellular microRNAs (miRNAs). The AM molecular machine consists
of two basic elements, one of which is a target-analogue-embedded
double-stem hairpin substrate (TDHS) and the other is a locking-strand-silenced
DNAzyme (LSDz). LSDz can be activated by target miRNA and catalytically
cleave TDHS, generating Clv-TDHS and releasing free target analogue
capable of triggering the next round of cleavage reaction. As such,
the molecular machine can exert sustainable autonomous operation,
producing an enhanced signal. Because the active target analogue comes
from the machine itself and offers cyclical stimulation in a feedback
manner, this target-induced autonomous cleavage circuit is termed
a self-feedback circuit (SFC). The SFC-based molecular machine can
be used to quantify miRNA-21 down to 10 pM without interference from
nontarget miRNAs, indicating a substantial improvement in assay performance
compared with its counterpart system without an SFC effect. Moreover,
due to the enzyme-free process, the AM molecular machine is suitable
for miRNA imaging in living cells, and the quantitative results are
consistent with the gold standard PCR assay. More interestingly, the
AM molecular machine can be used for the simultaneous fluorescence
imaging of several intracellular miRNAs, enabling the accurate discrimination
of cancerous cells (e.g., HeLa and MCF-7) from healthy cells. The
SFC-based autonomous-motion machine is expected to be a promising
tool for the research of molecular biology and early diagnosis of
human diseases.
DNA nanostructures have shown potential in cancer therapy. However, their clinical application is hampered by the difficulty to deliver them into cancer cells and susceptibility to nuclease degradation. To overcome these limitations, we report herein a periodically ordered nick‐hidden DNA nanowire (NW) with high serum stability and active targeting functionality. The inner core is made of multiple connected DNA double helices, and the outer shell is composed of regularly arranged standing‐up hairpin aptamers. All termini of the components are hidden from nuclease attack, whereas the target‐binding sites are exposed to allow delivery to the cancer target. The DNA NW remained intact during incubation for 24 h in serum solution. Animal imaging and cell apoptosis showed that NWs loaded with an anticancer drug displayed long blood‐circulation time and high specificity in inducing cancer‐cell apoptosis, thus validating this approach for the targeted imaging and therapy of cancers.
Based on the energy storage problem for solar energy utilization and the advantages of spiral groove tube heat exchanger, spiral groove tubes were used in the solar energy phase change heat storage. The thermal storage process of heat reservoir was simulated numerically. Firstly, the simulation method and the reliability of the used model are verified experimentally with smooth tube. Using spiral groove tube as water flow pipe and phase change material as heat storage medium, The three-dimensional model of heat storage was built by Gambit software and the grids were divided by ICEM. The heat storage process in the spiral groove tube and smooth tube heat storage were numerically simulated and the heat transfer enhancing effect was investigated. The influence of structural parameters such as groove pitch and groove depth on the heat storage process is simulated numerically and the influence rules are analyzed. The results show that the convective heat transfer intensity and heat transfer capability are enhanced when the smooth tubes are substituted by spiral groove tubes in the phase change heat storage and the heat storage time becomes shorter. In the range of this paper, the optimal structural parameters of spiral groove tube is groove pitch p=7mm and groove depth e=0.4mm.
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