A near-infrared light-responsive drug delivery platform based on Au–Ag nanorods (Au–Ag NRs) coated with DNA cross-linked polymeric shells was constructed. DNA complementarity has been applied to ...develop a polyacrylamide-based sol–gel transition system to encapsulate anticancer drugs into the gel scaffold. The Au–Ag NR-based nanogels can also be readily functionalized with targeting moieties, such as aptamers, for specific recognition of tumor cells. When exposed to NIR irradiation, the photothermal effect of the Au–Ag NRs leads to a rapid rise in the temperature of the surrounding gel, resulting in the fast release of the encapsulated payload with high controllability. In vitro study confirmed that aptamer-functionalized nanogels can be used as drug carriers for targeted drug delivery with remote control capability by NIR light with high spatial/temporal resolution.
Researchers increasingly envision an important role for artificial biochemical circuits in biological engineering, much like electrical circuits in electrical engineering. Similar to electrical ...circuits, which control electromechanical devices, biochemical circuits could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expressions in vivo. As a consequence of their relative robustness and potential applicability for controlling a wide range of in vitro chemistries, synthetic cell-free biochemical circuits promise to be useful in manipulating the functions of biological molecules. Here, we describe the first logical circuit based on DNA–protein interactions with accurate threshold control, enabling autonomous, self-sustained and programmable manipulation of protein activity in vitro. Similar circuits made previously were based primarily on DNA hybridization and strand displacement reactions. This new design uses the diverse nucleic acid interactions with proteins. The circuit can precisely sense the local enzymatic environment, such as the concentration of thrombin, and when it is excessively high, a coagulation inhibitor is automatically released by a concentration-adjusted circuit module. To demonstrate the programmable and autonomous modulation, a molecular circuit with different threshold concentrations of thrombin was tested as a proof of principle. In the future, owing to tunable regulation, design modularity and target specificity, this prototype could lead to the development of novel DNA biochemical circuits to control the delivery of aptamer-based drugs in smart and personalized medicine, providing a more efficient and safer therapeutic strategy.
In this aritcle, we have developed an interesting imaging method for intracellular ATP molecules with semiquantitation. While there has been a lot of work in understanding intracellular events, very ...few can come close to quantitation or semiquantitation in living cells. In this work, we made an effective use of nanomaterials, graphene oxides, both as a quencher and a carrier for intracellular delivery. In addition, this graphene oxide also serves as the carrier for reference probes for fluorescent imaging. An ATP aptamer molecular beacon (AAMB) is adsorbed on graphene oxide (GO) to form a double quenching platform. The AAMB/GO spontaneously enters cells, and then AAMB is released and opened by intracellular ATP. The resulting fluorescence recovery is used to perform ATP live-cell imaging with greatly improved background and signaling. Moreover, a control ssDNA, which is released nonspecifically from GO by nontarget cellular proteins, can serve as an internal reference for ATP semiquantification inside living cells using the intensity ratio of the AAMB and control. This approach can serve as a way for intracellular delivery and quantitative analysis.
AS1411 (previously known as AGRO100) is a 26 nucleotide guanine-rich DNA aptamer which forms a guanine quadruplex structure. AS1411 has shown promising utility as a treatment for cancers in Phase I ...and Phase II clinical trials without causing major side-effects. AS1411 inhibits tumor cell growth by binding to nucleolin which is aberrantly expressed on the cell membrane of many tumors. In this study, we utilized a simple technique to conjugate a widely-used chemotherapeutic agent, doxorubicin (Dox), to AS1411 to form a synthetic Drug-DNA Adduct (DDA), termed as AS1411-Dox. We demonstrate the utility of AS1411-Dox in the treatment of hepatocellular carcinoma (HCC) by evaluating the targeted delivery of Dox to Huh7 cells in vitro and in a murine xenograft model of HCC.
•The first study of using multi-scale simulation for H2 storage on Li doped g-C3N4.•The excess gravimetric density of H2 is about 4.50wt% at T=298K and P=100bar.•The g-C3N4 porous sheet shows ...advantages over MOFs and COFs.
Due to its porous structure and light mass the recently synthesized triazine-based graphitic C3N4 (g-C3N4) sheet is a promising material for gas storage. First-principles calculations based on density functional theory were used to study the hydrogen storage capacity of Li doped g-C3N4 under ambient thermodynamic conditions. The most stable binding site of Li atom on it is the open-hollow site with a binding energy of 3.26eV. Based on the force field parameters derived from quantum chemistry calculations, we have further performed grand canonical Monte Carlo (GCMC) simulations to investigate H2 adsorption isotherms on g-C3N4 sheet. We find that the adsorption energy of H2 is 3.48kcal/mol, and the excess uptake of hydrogen is about 4.50wt% at 298K and 100bar, showing potential as a hydrogen storage material.
Based on their enhanced cellular uptake, stability, biocompatibility, and versatile surface functionalization, spherical nucleic acids (SNAs) have become a potentially useful platform in biological ...applications. It still remains important to expand the SNAs’ “toolbox”, especially given the current interest in multimodal or theranostic nanomaterials, that is, composites capable of multiple simultaneous applications such as imaging, sensing, and drug delivery. In this paper, we have engineered a nanoparticle-conjugated initiator that triggers a cascade of hybridization reactions resulting in the formation of a long DNA polymer as the nanoparticle shell. By employing different DNA fragments, self-assembled multifunctional SNAs can be constructed. Therefore, using one capped ligand, these SNAs can combine imaging fluorescent tags, target recognition element, and targeted delivery molecules together. Since these SNAs possess high drug loading capacity and high specificity by the incorporation of an aptamer, our approach might find potential applications in new drug development, existing drug improvement, and drug delivery for cancer therapy.
Inspired by the recent experimental synthesis of graphene nanoribbons （GNKs） and theoretical research on their edge-decoration, we comprehensively studied the electrocatalytic performance of GNRs ...edge-decorated with Cu for CO2 reduction. Compared to zigzag GNRs, the Cu-terminated armchair GNRs with a width of n = 3p ＋ 2 were more efficient catalysts for producing methanol from CO2 with a free energy barrier of less than 0.5 eV, offering the advantages of a lower overpotential and higher selectivity than bulk Cu and other graphene-supported Cu structures. On the other hand, the competing hydrogen evolution reaction could be effectively suppressed by Cu-terminated armchair GNRs. Hence, the edge-decorated GNRs offer great flexibility for tuning the catalytic efficiency and selectivity for CO2 electroreduction.
Simultaneous monitoring of the expression, distribution, and dynamics of biological molecules in living cells is one of the most challenging tasks in the analytical sciences. The key to effective and ...successful intracellular imaging is the development of delivery platforms with high efficiency and ultrasensitive molecular probes for specific targets of interest. To achieve these goals, many nanomaterials are widely used as carriers to introduce nucleic acid probes into living cells for real-time imaging of biomolecules. However, limitations on their use include issues of cytotoxicity and delivery efficiency. Herein, we propose a switchable aptamer micelle flare (SAMF), formed by self-assembly of an aptamer switch probe–diacyllipid chimera, to monitor ATP molecules inside living cells. Similarity of hydrophobic composition between diacyllipids in the micelle flares and phospholipid bilayers in the dynamic membranes of living cells allows SAMFs to be uptaken by living cells more efficiently than aptamer switch probes without external auxiliary. Switchable aptamers were found to bind target ATP molecules with high selectivity and specificity, resulting in restoration of the fluorescence signal from “OFF” to “ON” state, thus indicating the presence of the analyte. These switchable aptamer micelle flares, which exhibit cell permeability and nanoscale controllability, show exceptional promise for molecular imaging in bioanalysis, disease diagnosis, and drug delivery.
Ionizable lipid nanocarriers have made historical contribution to COVID-19 mRNA vaccines. Here, we report ionizable polymeric nanoparticles that co-deliver bi-adjuvant and neoantigen peptides for ...cancer immunotherapy in combination with immune checkpoint blockade (ICB). Current cancer ICB benefits only a small subset of patients, largely due to a lack of pre-existing target cells and checkpoint targets for ICB, tumor antigenic heterogeneity, and tumor immunosuppression. Therapeutic vaccines hold the potential to enhance ICB therapeutic efficacy by expanding antitumor cell repertoires, upregulating immune checkpoint levels and hence sensitizing ICB, and reducing tumor immunosuppression. Chemically defined peptide vaccines are attractive, but their current therapeutic efficacy has been limited due to 1) poor vaccine delivery to immunomodulatory lymph nodes (LNs) and antigen (Ag)-presenting cells (APCs), 2) poor immunostimulant adjuvant efficacy with restricted target cell subsets in humans, 3) limited adjuvant/Ag codelivery to enhance Ag immunogenicity, and 4) limited ability to overcome tumor antigenic heterogeneity. Here, we developed nanovaccines (NVs) using pH-responsive polymeric micellular nanoparticles (NPs) for the codelivery of bi-adjuvant Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG and peptide neoantigens (neoAgs) to draining LNs for efficient Ag presentation in a broad range of APC subsets. These NVs potentiated the immunogenicity of peptide Ags and elicits robust antitumor T cell responses with memory, and remodeled the tumor immune milium with reduced tumor immunosuppression. As a result, NVs significantly enhanced ICB therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme (GBM). These results suggest marked potential of bi-adjuvant/neoAg-codelivering NVs for combination cancer immunotherapy.
Display omitted
•We developed nanovaccines that codeliver bi-adjuvant and neoantigen to potentiate antitumor immunity and tumor immunotherapy.•potentiate elicit robust antitumor T cell responses with memory, and remodel the tumor immune milium.•Enhanced the combination therapeutic efficacy for murine colorectal tumors and orthotopic glioblastoma multiforme.
The exploration of two-dimensional (2D) sheets beyond graphene has been gaining increasing interest. In this work, using first-principles calculations combined with grand canonical Monte Carlo (GCMC) ...simulations we systematically study the stability, electronic structure, optical absorbance and hydrogen adsorption of porphyrin (Por)-based nanosheets. We find these sheets to be thermally and mechanically stable. In addition, their electronic structure can be tuned from semiconducting to metallic by doping different metal atoms, and the sheets can absorb near infrared (NIR) light. We also calculate the hydrogen storage capacities of the MPor (M = Mg, Ca, Sc) at 298 K and 100 bar pressure and find that the hydrogen gravimetric density of ScPor nanosheet can reach 6.71 wt% which represents an enhancement of 45% as compared to the Sc-phthalocyanine sheet. The present study provides new insight into 2D organic nanostructures with potential applications.
PDF
