Dissipative operation of pH-responsive DNA-based nanodevices† † Electronic supplementary information (ESI) available. See DOI: 10.1039/d1sc03435a
Ontology highlight
ABSTRACT:
SUBMITTER: Mariottini D
PROVIDER: S-EPMC8442697 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Functional molecular nanodevices and nanomachines have attracted a growing interest for their potential use in life science and nanomedicine. In particular, due to their versatility and modularity DNA-based nanodevices appear extremely promising. However, a limitation of such devices is represented by the limited number of molecular stimuli and cues that can be used to control and regulate their function. Here we demonstrate the possibility to rationally control and regulate DNA-based nanodevices using biocatalytic reactions catalyzed by different enzymes. To demonstrate the versatility of our approach, we have employed three model DNA-based systems and three different enzymes (belonging to several classes, i.e., transferases and hydrolases). The possibility to use enzymes and enzymatic substrates as possible cues to operate DNA-based molecular nanodevices will expand the available toolbox of molecular stimuli to be used in the field of DNA nanotechnology and could open the door to many applications including enzyme-induced drug delivery and enzyme-triggered nanostructures assembly.
| S-EPMC4676031 | biostudies-literature
Project description:New methods for the preparation of reversible pH-responsive DNA hydrogels based on Hoogsteen triplex structures are described. One system consists of a hydrogel composed of duplex DNA units that bridge acrylamide chains at pH = 7.4 and undergoes dissolution at pH = 5.0 through the reconfiguration of one of the duplex bridging units into a protonated CG·C+ triplex structure. The second system consists of a hydrogel consisting of acrylamide chains crosslinked in the presence of an auxiliary strand by Hoogsteen TA·T triplex interaction at pH = 7.0. The hydrogel transforms into a liquid phase at pH = 10.0 due to the separation of the triplex bridging units. The two hydrogel systems undergo reversible and cyclic hydrogel/solution transitions by subjecting the systems to appropriate pH values. The anti-cancer drug, coralyne, binds specifically to the TA·T triplex-crosslinked hydrogel thereby increasing its stiffness. The pH-controlled release of the coralyne from the hydrogel is demonstrated.
| S-EPMC5707462 | biostudies-literature
Project description:Here we demonstrate that we can rationally and finely control the functionality of different DNA-based nanodevices and nanoswitches using electronic inputs. To demonstrate the versatility of our approach we have used here three different model DNA-based nanoswitches triggered by heavy metals and specific DNA sequences and a copper-responsive DNAzyme. To achieve electronic-induced control of these DNA-based nanodevices we have applied different voltage potentials at the surface of an electrode chip. The applied potential promotes an electron-transfer reaction that releases from the electrode surface a molecular input that ultimately triggers the DNA-based nanodevice. The use of electronic inputs as a way to finely activate DNA-based nanodevices appears particularly promising to expand the available toolbox in the field of DNA nanotechnology and to achieve a better hierarchical control of these platforms.
| S-EPMC5508672 | biostudies-literature
Project description:DNA nanotechnology enables straightforward fabrication of user-defined and nanometer-precise templates for a cornucopia of different uses. To date, most of these DNA assemblies have been static, but dynamic structures are increasingly coming into view. The programmability of DNA not only allows for encoding of the DNA object shape but also it may be equally used in defining the mechanism of action and the type of stimuli-responsiveness of the dynamic structures. However, these "robotic" features of DNA nanostructures are usually demonstrated for only small, discrete, and device-like objects rather than for collectively behaving higher-order systems. Here, we show how a large-scale, two-dimensional (2D) and pH-responsive DNA origami-based lattice can be assembled into two different configurations ("open" and "closed" states) on a mica substrate and further switched from one to the other distinct state upon a pH change of the surrounding solution. The control over these two configurations is achieved by equipping the arms of the lattice-forming DNA origami units with "pH-latches" that form Hoogsteen-type triplexes at low pH. In short, we demonstrate how the electrostatic control over the adhesion and mobility of the DNA origami units on the surface can be used both in the large lattice formation (with the help of directed polymerization) and in the conformational switching of the whole lattice. To further emphasize the feasibility of the method, we also demonstrate the formation of pH-responsive 2D gold nanoparticle lattices. We believe this work can bridge the nanometer-precise DNA origami templates and higher-order large-scale systems with the stimuli-induced dynamicity.
| S-EPMC10278177 | biostudies-literature
Project description:Aptamers that recognize specific cells in a complex environment have emerged as invaluable molecular tools in bioanalysis and in the development of targeted therapeutics. The selective recognition of aptamers, however, can be compromised by the coexistence of target receptors on both target cells and other cells. To address this problem, we constructed a structure-switchable aptamer (SW-Apt) with reconfigurable binding affinity in accordance with the microenvironment of target cells. The SW-Apt makes use of i-motifs, which are quadruplex structures that form in sequences rich in cytosine. More specifically, we report the design of single-stranded, pH-responsive i-motif-modified aptamers able to bind specifically with target cells by exploiting their pH. Here, the i-motif serves as a structural domain to either facilitate the binding ability of aptamers to target cells or suppress the binding ability of aptamers to nontarget cell based on the pH of the cellular microenvironment. SW-Apt exhibited high binding ability with target cells at acidic pH, while no obvious binding was observed at physiological pH. The i-motif-induced structure-switching was verified with Förster resonance energy transfer and circular dichroism spectroscopy. Notably, SW-Apt exhibits high specificity in serum and excellent stability, likely attributed to the folded quadruplex i-motif structure. This study provides a simple and efficient strategy to chemically modulate aptamer binding ability and thus improve aptamer binding specificity to target cells, irrespective of the coexistence of identical receptors on target and nontarget cells.
| S-EPMC6457906 | biostudies-literature
Project description:Cyclic dinucleotides (CDNs), such as c-di-GMP (CDG), are agonists for stimulator of interferon genes (STING) and are promising for cancer immunotherapy. Yet, the therapeutic efficacy of CDNs has been limited by poor delivery and biostability. Here, STING-activating DNA nanovaccines (STING-NVs) are developed, which biostabilize, deliver, and conditionally release CDG in the endosome of immune cells, elicit potent antitumor immune responses in murine and human immune cells, ameliorate immunosuppression in vitro and in the tumor microenvironment, and mediate potent cancer immunotherapy in a murine melanoma model. STING-NVs have PLA-b-PEG in the core and cytosine (C)-rich i-motif DNA on the surface. i-Motif DNA undergoes characteristic pH-responsive conformational switch, allowing efficient CDG loading via C:G base pairing at physiological pH, and CDG release in sensitive response to acidic environment such as cell endosome. STING-NVs protect CDG from enzymatic degradation. STING-NVs facilitate cell delivery. Remarkably, STING-NVs promote the endosome escape of CDG by ninefold, and potentiate antitumor immunity. STING-NVs repolarize immunosuppressive M2-like macrophages into antitumor M1-like macrophages in vitro and in the tumor microenvironment of melanoma. In a poorly immunogenic murine melanoma model, intralesional STING-NVs outperform liposomal CDG and fluoride-CDG for melanoma immunotherapy. These results suggest the great potential of STING-NVs for cancer immunotherapy.
| S-EPMC8323737 | biostudies-literature
Project description:The measurement of extracellular pH (pHe ) has significant clinical value for pathological diagnoses and for monitoring the effects of pH-altering therapies. One of the major problems of measuring pHe with a relaxation-based MRI contrast agent is that the longitudinal relaxivity depends on both pH and the concentration of the agent, requiring the use of a second pH-unresponsive agent to measure the concentration. Here we tested the feasibility of measuring pH with a relaxation-based dendritic MRI contrast agent in a concentration-independent manner at clinically relevant field strengths. The transverse and longitudinal relaxation times in solutions of the contrast agent (GdDOTA-4AmP)44 -G5, a G5-PAMAM dendrimer-based MRI contrast agent in water, were measured at 3 T and 7 T magnetic field strengths as a function of pH. At 3 T, longitudinal relaxivity (r1 ) increased from 7.91 to 9.65 mM(-1) s(-1) (on a per Gd(3+) basis) on changing pH from 8.84 to 6.35. At 7 T, r1 relaxivity showed pH response, albeit at lower mean values; transverse relaxivity (r2 ) remained independent of pH and magnetic field strengths. The longitudinal relaxivity of (GdDOTA-4AmP)44 -G5 exhibited a strong and reversible pH dependence. The ratio of relaxation rates R2 /R1 also showed a linear relationship in a pH-responsive manner, and this pH response was independent of the absolute concentration of (GdDOTA-4AmP)44 -G5 agent. Importantly, the nanoprobe (GdDOTA-4AmP)44 -G5 shows pH response in the range commonly found in the microenvironment of solid tumors.
| S-EPMC4713357 | biostudies-literature
Project description:Differences in pH between the tumour interstitium and healthy tissues can be used to induce conformational changes in the nanocarrier structure, thereby triggering drug release at the desired site. In the present study, novel pH-responsive nanocarriers were developed by modifying conventional niosomes with hexadecyl-poly(acrylic acid)n copolymers (HD-PAAn). Niosomal vesicles were prepared by the thin film hydration method using Span 60, Span 60/Tween 60 and cholesterol as main constituents, and HD-PAA modifiers of different concentrations (0.5, 1, 2.5, 5 mol%). Next, two model substances, a water-soluble fluorescent dye (calcein) and a hydrophobic agent with pronounced antineoplastic activity (curcumin), were loaded in the aqueous core and hydrophobic membrane of the elaborated niosomes, respectively. Physicochemical properties of blank and loaded nanocarriers such as hydrodynamic diameter (Dh), size distribution, zeta potential, morphology and pH-responsiveness were investigated in detail. The cytotoxicity of niosomal curcumin was evaluated against human malignant cell lines of different origins (MJ, T-24, HUT-78), and the mechanistic aspects of proapoptotic effects were elucidated. The formulation composed of Span 60/Tween 60/cholesterol/2.5% HD-PAA17 exhibited optimal physicochemical characteristics (Dh 302 nm; ζ potential -22.1 mV; high curcumin entrapment 83%), pH-dependent drug release and improved cytotoxic and apoptogenic activity compared to free curcumin.
| S-EPMC11008427 | biostudies-literature
Project description:Cellular reporters of enzyme activity are based on either fluorescent proteins or small molecules. Such reporters provide information corresponding to wherever inside cells the enzyme is maximally active and preclude minor populations present in subcellular compartments. Here we describe a chemical imaging strategy to selectively interrogate minor, subcellular pools of enzymatic activity. This new technology confines the detection chemistry to a designated organelle, enabling imaging of enzymatic cleavage exclusively within the organelle. We have thus quantitatively mapped disulfide reduction exclusively in endosomes in Caenorhabditis elegans and identified that exchange is mediated by minor populations of the enzymes PDI-3 and TRX-1 resident in endosomes. Impeding intra-endosomal disulfide reduction by knocking down TRX-1 protects nematodes from infection by Corynebacterium diphtheriae, revealing the importance of this minor pool of endosomal TRX-1. TRX-1 also mediates endosomal disulfide reduction in human cells. A range of enzymatic cleavage reactions in organelles are amenable to analysis by this new reporter strategy.
| S-EPMC6859052 | biostudies-literature
Project description:Synthetic nanoscale devices that reconfigure dynamically in response to physiological stimuli could offer new avenues for diagnostics and therapy. Here, we report a strategy for controlling the state of DNA nanodevices based on sensing antigens with IgG antibodies. To this end, we use IgG antibodies as structural elements to kinetically trap reconfigurable DNA origami structures in metastable states. Addition of soluble antigens displace the IgGs from the objects and triggers reconfiguration. We demonstrate this mechanism by antigen-triggered disassembly of DNA origami shells for two different IgGs and their cognate antigens, and we determined the corresponding dose response curves. We also describe the logic-gated actuation of DNA objects with combinations of antigens, as demonstrated with AND-type shells that disassemble only when two different antigens are detected simultaneously. We apply our system for the antigen-triggered release of molecular payload as exemplified by the release of virus particles that we loaded into the DNA origami shells. We expect our approach to be applicable in many types of DNA nanostructures and with many other IgG-antigen combinations.
| S-EPMC8719334 | biostudies-literature