Organic Spherical Nucleic Acids for the Transport of a NIR-II-Emitting Dye Across the Blood-Brain Barrier.

DNA nanotechnology plays an increasingly important role in the biomedical field; however, its application in the design of organic nanomaterials is underexplored. Herein, we report the use of DNA nanotechnology to transport a NIR-II-emitting nanofluorophore across the blood-brain barrier (BBB), facilitating non-invasive imaging of brain tumors. Specifically, the DNA block copolymer, PS-b-DNA, is synthesized through a solid-phase click reaction. We demonstrate that its self-assembled structure shows exceptional cluster effects, among which BBB-crossing is the most notable. Therefore, PS-b-DNA is utilized as an amphiphilic matrix to fabricate a NIR-II nanofluorephore, which is applied in in vivo bioimaging. Accordingly, the NIR-II fluorescence signal of the DNA-based nanofluorophore localized at a glioblastoma is 3.8-fold higher than the NIR-II fluorescence signal of the PEG-based counterpart. The notably increased imaging resolution will significantly benefit the further diagnosis and therapy of brain tumors.

A self-delivery DNA nanoprobe for reliable microRNA imaging in live cells by aggregation induced red-shift-emission.

A new DNA nanoprobe based on a Y-shape and pyrene-modified DNA self-assembly is developed to sensitively and specifically detect microRNA through a pyrene excimer-monomer switch. Exhibiting the capability of self-delivery and resistance to nuclease degradation, the nanoprobe has been successfully applied for microRNA imaging in live cells.

Rational Design of Smart Hydrogels for Biomedical Applications.

Hydrogels are polymeric three-dimensional network structures with high water content. Due to their superior biocompatibility and low toxicity, hydrogels play a significant role in the biomedical fields. Hydrogels are categorized by the composition from natural polymers to synthetic polymers. To meet the complicated situation in the biomedical applications, suitable host-guest supramolecular interactions are rationally selected. This review will have an introduction of hydrogel classification based on the formulation molecules, and then a discussion over the rational design of the intelligent hydrogel to the environmental stimuli such as temperature, irradiation, pH, and targeted biomolecules. Further, the applications of rationally designed smart hydrogels in the biomedical field will be presented, such as tissue repair, drug delivery, and cancer therapy. Finally, the perspectives and the challenges of smart hydrogels will be outlined.

Magnesium-Stabilized Multifunctional DNA Nanoparticles for Tumor-Targeted and pH-Responsive Drug Delivery.

Functional nucleic acids, which can target cancer cells and realize stimuli-responsive drug delivery in tumor microenvironment, have been widely applied for anticancer chemotherapy. At present, high cost, unsatisfactory biostability, and complicated fabrication process are the main limits for the development of DNA-based drug-delivery nanocarriers. Here, a doxorubicin (Dox)-delivery nanoparticle for tumor-targeting chemotherapy is developed taking advantage of rolling circle amplification (RCA) technique, by which a high quantity of functional DNAs can be efficiently collected. Furthermore, Mg2+, a major electrolyte in human body showing superior biocompatibility, can sufficiently condense the very long sequence of an RCA product and better preserve its functions. The resultant DNA nanoparticle exhibits a high biostability, making it a safe and ideal nanomaterial for in vivo application. Through cellular and in vivo experiments, we thoroughly demonstrate that this kind of Mg2+-stabilized multifunctional DNA nanoparticles can successfully realize tumor-targeted Dox delivery. Overall, exploiting RCA technique and Mg2+ condensation, this new strategy can fabricate nanoparticles with a nontoxic composition through a simple fabrication process and provides a good way to preserve and promote DNA functions, which will show a broad application potential in the biomedical field.

A controllable aptamer-based self-assembled DNA dendrimer for high affinity targeting, bioimaging and drug delivery.

Targeted drug delivery is important in cancer therapy to decrease the systemic toxicity resulting from nonspecific drug distribution and to enhance drug delivery efficiency. We have developed an aptamer-based DNA dendritic nanostructure as a multifunctional vehicle for targeted cancer cell imaging and drug delivery. The multifunctional DNA dendrimer is constructed from functional Y-shaped building blocks with predesigned base-pairing hybridization including fluorophores, targeting DNA aptamers and intercalated anticancer drugs. With controllable step-by-step self-assembly, the programmable DNA dendrimer has several appealing features, including facile modular design, excellent biostability and biocompatibility, high selectivity, strong binding affinity, good cell internalization efficiency, and high drug loading capacity. Due to the unique structural features of DNA dendrimers, multiple copies of aptamers can be incorporated into each dendrimer, generating a multivalent aptamer-tethered nanostructure with enhanced binding affinity. A model chemotherapeutic anticancer drug, doxorubicin, was delivered via these aptamer-based DNA dendrimers and exerted a potent toxicity for target cancer cells (human T cell acute lymphoblastic leukemia cell line) with low side effects for the non-target cells (human Burkitt's lymphoma cell line). This controllable aptamer-based DNA dendrimer is a promising candidate for biomedical applications.

Highly sensitive and selective detection of miRNA: DNase I-assisted target recycling using DNA probes protected by polydopamine nanospheres.

Based on the protective properties of polydopamine nanospheres for DNA probes against nuclease digestion, we have developed a DNase I-assisted target recycling signal amplification method for highly sensitive and selective detection of miRNA.

Graphene oxide protected nucleic acid probes for bioanalysis and biomedicine.

Recently, the binding ability of DNA on GO and resulting nuclease resistance have attracted increasing attention, leading to new applications both in vivo and in vitro. In vivo, nucleic acids absorbed on GO can be effectively protected from enzymatic degradation and biological interference in complicated samples, making it useful for targeted delivery, gene regulation, intracellular detection and imaging with high uptake efficiencies, high intracellular stability, and very low toxicity. In vitro, the adsorption of ssDNA on GO surface and desorption of dsDNA or well-folded ssDNA from GO surface result in the protection and deprotection of DNA from nucleic digestion, respectively, which has led to target-triggered cyclic enzymatic amplification methods (CEAM) for amplified detection of analytes with sensitivity 2-3 orders of magnitude higher than that of 1:1 binding strategies. This Concept article explores some of the latest developments in this field.

Target-responsive "sweet" hydrogel with glucometer readout for portable and quantitative detection of non-glucose targets.

Portable devices with the advantages of rapid, on-site, user-friendly, and cost-effective assessment are widely applied in daily life. However, only a limited number of quantitative portable devices are commercially available, among which the personal glucose meter (PGM) is the most successful example and has been the most widely used. However, PGMs can detect only blood glucose as the unique target. Here we describe a novel design that combines a glucoamylase-trapped aptamer-cross-linked hydrogel with a PGM for portable and quantitative detection of non-glucose targets. Upon target introduction, the hydrogel collapses to release glucoamylase, which catalyzes the hydrolysis of amylose to produce a large amount of glucose for quantitative readout by the PGM. With the advantages of low cost, rapidity, portability, and ease of use, the method reported here has the potential to be used by the public for portable and quantitative detection of a wide range of non-glucose targets.

Astringinin-mediated attenuation of the hepatic injury following trauma-hemorrhage.

Although astringinin administration under adverse circulatory conditions is known to be protective, the mechanism by which astringinin produces the salutary effects remains unknown. We hypothesize that astringinin administration in males following trauma-hemorrhage decreases cytokine production and protects against hepatic injury. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure: 40 mmHg for 90 min, then resuscitation). Different doses of astringinin (0.01, 0.03, 0.1, 0.3 mg/kg of body weight) or vehicle were administered intravenously during resuscitation. Concentrations of plasma aspartate aminotransferase (AST) with alanine aminotransferase (ALT) and various hepatic parameters were measured (n = 8 rats/group) at 24 h after resuscitation. One-way ANOVA and Tukey testing were used for statistical analysis. Trauma-hemorrhage significantly increased plasma AST and ALT levels at 24 h postresuscitation; there was a dose-related benefit when astringinin was administered at doses of 0.01 to 0.3 mg/kg. In astringinin-treated (0.3 mg/kg) rats subjected to trauma-hemorrhage, there were significant improvements in liver myeloperoxidase (MPO) activity (237.80 +/- 45.89 vs. 495.95 +/- 70.64 U/mg protein, P < 0.05), interleukin-6 (IL-6) levels (218.54 +/- 34.52 vs. 478.60 +/- 76.21 pg/mg protein, P < 0.05), cytokine-induced neutrophil chemoattractant (CINC)-1 (88.32 +/- 20.33 vs. 200.70 +/- 32.68 pg/mg protein, P < 0.05), CINC-3 (110.83 +/- 26.63 vs. 290.14 +/- 76.82 pg/mg protein, P < 0.05) and intercellular adhesion molecule (ICAM)-1 concentrations (1,868.5 +/- 211.5 vs. 3,645.0 +/- 709.2 pg/mg protein, P < 0.05), as well as in histology. Results show that astringinin significantly attenuates proinflammatory responses and hepatic injury after trauma-hemorrhage. In conclusion, the salutary effects of astringinin administration on attenuation of hepatic injury following trauma-hemorrhage are likely due to reduction of pro-inflammatory mediator levels.