Stimuli-Responsive mRNA Vaccines to Induce Robust CD8+ T Cell Response via ROS-Mediated Innate Immunity Boosting.

The messenger RNA (mRNA) vaccines hold great significance in contagion prevention and cancer immunotherapy. However, safely and effectively harnessing innate immunity to stimulate robust and durable adaptive immune protection is crucial, yet challenging. In this study, we synthesized a library of stimuli-responsive bivalent ionizable lipids (srBiv iLPs) with smart molecular blocks responsive to esterase, H2O2, cytochrome P450, alkaline phosphatase, nitroreductase, or glutathione (GSH), aiming to leverage physiological cues to trigger fast lipid degradation, promote mRNA translation, and induce robust antitumor immunity via reactive oxygen species (ROS)-mediated boosting. After subcutaneous immunization, esterase-responsive vaccine (eBiv-mVac) was rapidly internalized and transported into the draining lymph nodes. It then underwent fast decaging and self-immolative degradation in esterase-rich antigen-presenting cells, releasing sufficient mRNA for antigen translation and massive reactive quinone methides to elevate ROS levels. This resulted in broad activation of innate immunity to boost T cell response, prompting a large number of primed antigen-specific CD8+ T cells to circulate and infiltrate into tumors (>1000-fold versus unvaccinated control), thereby orchestrating innate and adaptive immunity to control tumor growth. Moreover, by further combining our vaccination strategy with immune checkpoint blockade, we demonstrated a synergism that significantly amplified the magnitude and function of antigen-specific CD8+ T cells. This, in turn, caused potent systemic antitumor efficacy and prolonged survival with high complete response rate in xenograft and metastasis models. Overall, our generalized stimuli-responsive mRNA delivery platform promises a paradigm shift in the design of potent vaccines for cancer immunotherapy, as well as effective and precise carriers for gene editing, protein replacement, and cell engineering.

Tunable Multivalent Aptamer-Based DNA Nanostructures To Regulate Multiheteroreceptor-Mediated Tumor Recognition.

Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.

Selenium yeast improve growth, serum biochemical indices, metabolic ability, antioxidant capacity and immunity in black carp Mylopharyngodnpiceus.

This experiment was conducted to investigate the impacts of dietary selenium yeast (SeY) on the growth performance, fish body composition, metabolic ability, antioxidant capability, immunity and inflammatory responses in juvenile black carp (Mylopharyngodn piceus). The base diet was supplemented with 0.00, 0.30 and 0.60 g/kg SeY (0.04, 0.59 and 1.15 mg/kg of selenium) to form three isonitrogenous and isoenergetic diets for juvenile black carp with a 60-day. Adequate dietary SeY (0.30 and 0.60 g/kg) could significantly increase the weight gain (WG), special growth rate (SGR) compared to the SeY deficient groups (0.00 g/kg) (P < 0.05). Meanwhile, 0.30 and 0.60 g/kg SeY elevated the mRNA levels of selenoprotein T2 (SEPT2), selenoprotein H (SEPH), selenoprotein S (SEPS) and selenoprotein M (SEPM) in the liver and intestine compared with the SeY deficient groups (P < 0.05). Adequate dietary SeY could promote glucose catabolism and utilization through activating glucose transport (GLUT2), glycolysis (GCK, HK, PFK, PK, PDH), tricarboxylic acid cycle (ICDH and MDH), glycogen synthesis (LG, GCS and GBE) and IRS/PI3K/AKT signal pathway molecules (IRS2b, PI3Kc and AKT1) compared with the SeY deficient groups (P < 0.05). Similarly, adequate dietary SeY could improve lipid transport and triglycerides (TG) synthesis through increasing transcription amounts of CD36, GK, DGAT, ACC and FAS in the fish liver compared with the SeY deficient groups (P < 0.05). In addition, adequate SeY could markedly elevate activities of antioxidant enzymes (T-SOD, CAT, GR, GPX) and contents of T-AOC and GSH, while increased transcription amounts of Nrf2, Cu/Zn-SOD, CAT, and GPX in fish liver and intestine (P < 0.05). However, adequate SeY notably decreased contents of MDA, and the mRNA transcription levels of Keap1 in the intestine compared with the SeY deficient groups (P < 0.05). Adequate SeY markedly increased amounts or levels of the immune factors (ALP, ACP, LZM, C3, C4 and IgM) and the transcription levels of innate immune-related functional genes in the liver and intestine (LZM, C3 and C9) compared to the SeY deficient groups (P < 0.05). Moreover, adequate SeY could notably reduce levels of IL-8, IL-1ß, and IFN-γ and elevate TGF-1ß levels in fish intestine (P < 0.05). The transcription levels of MAPK13, MAPK14 and NF-κB p65 were notably reduced in fish intestine treated with 0.30 and 0.60 g/kg SeY (P < 0.05). In conclusion, these results suggested that 0.30 and 0.60 g/kg SeY could not only improve growth performance, increase Se, glucose and lipid metabolic abilities, enhance antioxidant capabilities and immune responses, but also alleviate inflammation, thereby supplying useful reference for producing artificial feeds in black carp.

Orthogonal retrieval algorithm of atmospheric temperature profiles from pure rotational Raman lidar signals.

Aimed at the stability of calibration coefficients in a general non-orthogonal retrieval algorithm (NRA) of pure rotational Raman lidars (PRRLs), an orthogonal retrieval algorithm (ORA) of atmospheric temperature profiles based on the orthogonal basis function is proposed. This algorithm eliminates the correlation between the calibration coefficients in the NRA to reduce the influence of the number of calibration points and the selection scheme on the calibration coefficients. In this paper, the stabilities of calibration coefficients in the NRA and ORA are compared and analyzed, and the data analysis for atmospheric temperature profiles with a time resolution of minute-level are given, based on the developed Cloud Precipitation Potential Evaluation (CPPV) lidar data and the parallel radiosonde temperature data. The analysis results show that coefficients of variation (CVs) of ORA calibration coefficients are one order of magnitude smaller than those of NRA coefficients. The mean deviation of the ORA retrieval results is roughly reduced by 16.1% compared with the NRA, and the root-mean-square deviation is roughly reduced by 15.0% compared with the NRA. Therefore, the temperature retrieval performance of the ORA is better than that of the NRA.

Novel Ultralow-Potential Electrochemiluminescence Aptasensor for the Highly Sensitive Detection of Zearalenone Using a Resonance Energy Transfer System.

An ultralow-potential electrochemiluminescence (ECL) aptasensor has been designed for zearalenone (ZEN) assay based on a resonance energy transfer (RET) system with SnS2 QDs/g-C3N4 as a novel luminophore and CuO/NH2-UiO-66 as a dual-quencher. SnS2 QDs were loaded onto g-C3N4 nanosheets and enhanced the ECL luminescence via strong synergistic effects under an ultralow potential. The UV-vis absorption spectrum of CuO/NH2-UiO-66 exhibits considerable overlap with the ECL emission spectrum of SnS2 QDs/g-C3N4, an important consideration for the RET process. In order to stimulate RET, the ZEN aptamer and complementary DNA are introduced for conjugation between the donor and the acceptor. With the binding interaction between ZEN by its aptamer, CuO/NH2-UiO-66 is removed from the electrode surface, resulting in the inhibition of the RET system and an increase in the ECL signal. Under optimal conditions, the as-prepared aptasensor quantified ZEN from 0.5 µg·mL-1 to 0.1 fg·mL-1 with a low limit of detection of 0.085 fg·mL-1, and it exhibited good stability, excellent specificity, high reproducibility, and desirable practicality. The sensing strategy provides a method for mycotoxins assay to monitor food safety.

Serendipita indica chitinase protects rice from the blast and bakanae diseases.

Serendipita indica, a multifunctional and useful endophyte fungus, has been intensively investigated in promoting plant growth and resistance towards biotic and abiotic stress. Multiple chitinases from microorganisms or plants have been identified to have a high antifungal activity as a biological control. However, chitinase of S. indica still needs to be characterized. We functionally characterized a chitinase (SiChi) in S. indica. The result showed that the purified SiChi protein confers high chitinase activity; importantly, SiChi inhibits the conidial germination of Magnaporthe oryzae and Fusarium moniliforme. After the successful colonization of rice roots by S. indica, both the rice blast disease and bakanae disease were significantly reduced. Interestingly, the purified SiChi could promptly induce rice disease resistance towards M. oryzae and F. moniliforme pathogens when sprayed on rice leaves. Like S. indica, SiChi could upregulate rice pathogen-resistant proteins and defense enzymes. In conclusion, chitinase of S. indica has direct antifungal activity and indirect induced resistance activity, implying an efficient and economic strategy for rice disease control by applying S. indica and SiChi.

Stimuli-Responsive PROTACs for Controlled Protein Degradation.

Proteolysis Targeting Chimeras (PROTACs) represent a promising therapeutic modality to address undruggable and resistant issues in drug discovery. However, potential on-target toxicity remains clinically challenging. We developed a generalized caging strategy to synthesize a series of stimuli-responsive PROTACs (sr-PROTACs) with diverse molecular blocks bearing robust and cleavable linkers, presenting "turn on" features in manipulating protein degradation. By leveraging pathological cues, such as elevated ROS, phosphatase, H2 S, or hypoxia, and external triggers, such as ultraviolet light, X-Ray, or bioorthogonal reagents, we achieved site-specific activation and traceless release of original PROTACs through de-caging and subsequent self-immolative cleavage, realizing selective uptake and controlled protein degradation in vitro. An in vivo study revealed that two sr-PROTACs with phosphate- and fluorine-containing cages exhibited high solubility and long plasma exposure, which were specifically activated by tumor overexpressing phosphatase or low dosage of X-Ray irradiation in situ, leading to efficient protein degradation and potent tumor remission. With more reactive biomarkers to be screened from clinical practice, our caging library could provide a general tool to design activatable PROTACs, prodrugs, antibody-drug conjugates, and smart biomaterials for personalized treatment, tissue engineering or regenerative medicine.

De Novo design of a humanized antiCD33 antibody-oridonin conjugate for acute myeloid leukemia therapy.

Acute myeloid leukemia (AML) is the most common blood cancer in adults. Patients' 5-year overall survival is less than 30% thus having a poor prognosis. To date, the development of novel target therapies is still necessary to ameliorate patients' survival. Antibody-drug conjugates (ADCs) represent a promising class of drugs for the treatment of AML. CD33 is highly expressed on AML cells, and the FDA-approved CD33-targeted ADC drug-gemtuzumab ozogamicin (GO) has proved the feasibility of CD33-targeted ADC drug design. In this study, we constructed a novel CD33-targeted ADC drug composed of a humanized anti-CD33 antibody and oridonin as a payload with a cleaved chemical linker. Oridonin is a natural product that has great cancer therapy potential while its poor bioavailability and targeting ability limited its clinical use. Herein, we demonstrated that antiCD33-oridonin specifically delivered oridonin in AML cells improved AML cells killing ability of oridonin. Meanwhile, it did not show any non-specific toxicity on CD33 negative cells. In summary, we developed a novel AML targeting ADC with clinical application potential, and therefore provided a new solution for the druggability improvement of oridonin.

Self-Healing and Shape Memory Hypercrosslinked Metal-Organic Polyhedra Polymers via Coordination Post-Assembly.

Coordination-driven crosslinking networks with reversible and dynamic characteristics are gaining increasing interest in diverse application fields. Herein, we use a coordination crosslinking approach using metal-organic polyhedra (MOPs) as high-connectivity building blocks to post-assemble a class of coordination hypercrosslinked MOP (CHMOP) polymers. The introduction of 12-connected MOP nodes to the polymeric networks is critical to producing membranes that overcome the trade-off between mechanical properties and dynamic healing, and meanwhile possess multifunctionalities including shape memory, solution processability, and 3D printing. The CHMOPs can also be used for anticorrosion coating and achieve function couplings, e.g., shape memory-assisted self-healing (SMASH), which have not been achieved in the MOP-based hybrid materials yet. This work not only offers a feasible strategy to construct new multifunctional materials but also greatly expands the application scopes of MOPs.

Fabricating Industry-Compatible Olefin-Linked COF Resins for Oxoanion Pollutant Scavenging.

Large-scale and low-cost synthesis of covalent organic frameworks (COFs) to meet the demands of industrial application remains formidably challenge. Here we report using 2,4,6-collidine as monomer to produce a series of highly crystalline olefin-linked COFs by a melt polymerization method. This method enables the kilogram-scale fabrication of self-shaped monolithic robust foams. The afforded COFs possess extremely low cost (<50 USD/kg), superior to all the reported COFs. Furthermore, using one-pot or post-modification methods can conveniently transform neutral COFs to ionic COFs, which can be applied as highly efficient ion-exchange sorbents for scavenging oxoanion pollutants. Remarkably, the superior adsorption capacity of a model oxoanion (ReO4 - ) is the highest among crystalline porous materials reported so far. This work not only expands the scopes of olefin-linked COFs but also enlightens the route for the industrial production of crystalline ion exchange sorbents.

Noggin, an inhibitor of bone morphogenetic protein signaling, antagonizes TGF-ß1 in a mouse model of osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide; however, disease-modifying treatments are lacking because of the complicated pathological mechanisms. As a breakthrough, aberrant activation of transforming growth factor-ß 1 (TGF-ß1)in subchondral bone has been confirmed as an essential pathomechanism for OA progression, and has become a potential therapeutic target. In addition to R&D on neutralizing antibodies, small-molecule antagonists and chemical medicines, native antagonists of TGF-ß1 could be exploited as another promising approach. Noggin (NOG) is an antagonist of bone morphogenetic proteins (BMPs) and was reported to effectively attenuate OA by protecting cartilage and preventing pathological subchondral bone remodeling. However, the underlying mechanisms have not been fully clarified. We first detected the distribution of NOG in knee joints of an OA mouse model, which showed upregulation at early stage of OA but downregulation later in the subchondral bone and no significant change in the articular cartilage. Furthermore, the interaction between NOG and TGF-ß1 was verified, which in turn suppressed the downstream SMAD2/3 activity of TGF-ß1. Moreover, the proliferation and chondrogenesis of mesenchymal stem cells (MSCs) were not significantly influenced by NOG. Taken together, the results showed that NOG antagonized TGF-ß1 but did not repress MSC proliferation and chondrogenesis; thus, it seems promising for OA treatment.

Effects of different types of humic acid isolated from coal on soil NH3 volatilization and CO2 emissions.

Humic acid can improve soil nutrients and promote plant growth. Weathered coal and lignite can be used as agricultural resources due to high humic acid content, but their impact on soil NH3 volatilization and CO2 emissions are yet to be determined. In this study, a field experiment was carried out to compare the effects of four types of humic acid isolated from coal (pulverized weathered coal (HC), pulverized lignite (HL), alkalized weathered coal (AC) and alkalized lignite (AL)) on NH3 volatilization, CO2 emissions, pH, the C/N ratio and enzyme activities in soil cultivated with maize. The effect of biotechnology humic acids (BHA) was also examined for comparison. HL, AC, AL and BHA all increased cumulative NH3 losses by 147.7, 278.5, 113.9, and 355.3%, respectively, compared with the control (chemical fertilizer only), and notably, BHA caused an increase of 90.71% compared with the humic acids isolated from coal. A significant increase in cumulative CO2 losses was observed only under AL treatment, by 14.44-24.90% compared with all other treatments. Soil urease activity was positively correlated with cumulative NH3 losses (P < 0.001), while the soil C/N ratio (P < 0.001) and soil sucrase activity (P < 0.05) were positively correlated with cumulative CO2 losses. Since humic acid from pulverized weathered coal caused no increase in NH3 volatilization or CO2 emissions, it is therefore thought to be the most suitable humic acid for field application.

Grotthuss Proton-Conductive Covalent Organic Frameworks for Efficient Proton Pseudocapacitors.

Herein, we describe the synthesis of two highly crystalline, robust, hydrophilic covalent organic frameworks (COFs) that display intrinsic proton conduction by the Grotthuss mechanism. The enriched redox-active azo groups in the COFs can undergo a proton-coupled electron transfer reaction for energy storage, making the COFs ideal candidates for pseudocapacitance electrode materials. After in situ hybridization with carbon nanotubes, the composite exhibited a high three-electrode specific capacitance of 440 F g-1 at the current density of 0.5 A g-1 , among the highest for COF-based supercapacitors, and can retain 90 % capacitance even after 10 000 charge-discharge cycles. This is the first example using Grotthuss proton-conductive organic materials to create pseudocapacitors that exhibited both high power density and energy density. The assembled asymmetric two-electrode supercapacitor showed a maximum energy density of 71 Wh kg-1 with a maximum power density of 42 kW kg-1 , surpassing that of all reported COF-based systems.

Histone Deacetylase Inhibitor SAHA Improves High Salinity Tolerance Associated with Hyperacetylation-Enhancing Expression of Ion Homeostasis-Related Genes in Cotton.

Histone acetylation plays an important role in regulation of chromatin structure and gene expression in terms of responding to abiotic stresses. Histone acetylation is modulated by histone deacetylases (HDACs) and histone acetyltransferases. Recently, the effectiveness of HDAC inhibitors (HDACis) for conferring plant salt tolerance has been reported. However, the role of HDACis in cotton has not been elucidated. In the present study, we assessed the effects of the HDACi suberoylanilide hydroxamic acid (SAHA) during high salinity stress in cotton. We demonstrated that 10 µM SAHA pretreatment could rescue of cotton from 250 mM NaCl stress, accompanied with reduced Na+ accumulation and a strong expression of the ion homeostasis-related genes. Western blotting and immunostaining results revealed that SAHA pretreatment could induce global hyperacetylation of histone H3 at lysine 9 (H3K9) and histone H4 at lysine 5 (H4K5) under 250 mM NaCl stress, indicating that SAHA could act as the HDACi in cotton. Chromatin immunoprecipitation and chromatin accessibility coupled with real time quantitative PCR analyses showed that the upregulation of the ion homeostasis-related genes was associated with the elevated acetylation levels of H3K9 and H4K5 and increased chromatin accessibility on the promoter regions of these genes. Our results could provide a theoretical basis for analyzing the mechanism of HDACi application on salt tolerance in plants.

Combined Intrinsic and Extrinsic Proton Conduction in Robust Covalent Organic Frameworks for Hydrogen Fuel Cell Applications.

Developing new materials for the fabrication of proton exchange membranes (PEMs) for fuel cells is of great significance. Herein, a series of highly crystalline, porous, and stable new covalent organic frameworks (COFs) have been developed by a stepwise synthesis strategy. The synthesized COFs exhibit high hydrophilicity and excellent stability in strong acid or base (e.g., 12 m NaOH or HCl) and boiling water. These features make them ideal platforms for proton conduction applications. Upon loading with H3 PO4 , the COFs (H3 PO4 @COFs) realize an ultrahigh proton conductivity of 1.13×10-1  S cm-1 , the highest among all COF materials, and maintain high proton conductivity across a wide relative humidity (40-100 %) and temperature range (20-80 °C). Furthermore, membrane electrode assemblies were fabricated using H3 PO4 @COFs as the solid electrolyte membrane for proton exchange resulting in a maximum power density of 81 mW cm-2 and a maximum current density of 456 mA cm-2 , which exceeds all previously reported COF materials.

Mathematical models of amino acid panel for assisting diagnosis of children acute leukemia.

BACKGROUND: The altered concentrations of amino acids were found in the bone marrow or blood of leukemia patients. Metabolomics technology combining mathematical model of biomarkers could be used for assisting the diagnosis of pediatric acute leukemia (AL). METHODS: The concentrations of 17 amino acids was measured by targeted liquid chromatograph-tandem mass spectrometry in periphery blood collected using dried blood spots. After evaluation, the mathematical models were further evaluated by prospective clinical validation cohort for AL diagnosis. RESULTS: The concentrations of 13 in 17 amino acids were statistically different between the periphery blood dried serum dots measured by targeted LC-MS/MS. The receiver operating characteristic analysis for the models of amino acid panel showed that the area under curve for AL diagnosis were 0.848, 0.834 and 0.856 by SVM, RF and XGBoost. The Kappa values in further prospectively evaluated clinical cohort were 0.697, 0.703 and 0.789 (p > 0.05) respectively, and the accuracies for the models were 84.86%, 85.20% and 89.46% respectively with further clinical validation. CONCLUSIONS: The established mathematical model is a faster, cheaper and more convenient way than conventional methods, and no significant difference on the effect of diagnosis comparing with conventional methods. The mathematical model can be clinically useful for assisting pediatric AL diagnosis.

Modulating Aptamer Specificity with pH-Responsive DNA Bonds.

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.

A comparative study of single-stage transpedicular debridement, fusion, and posterior long-segment versus short-segment fixation for the treatment of thoracolumbar spinal tuberculosis in adults: minimum five year follow-up outcomes.

DESIGN: This a retrospective study in single centre. OBJECTIVE: The objective of this retrospective clinical study is to compare the long-term clinical efficacy of posterior long-segment and short-segment fixation with single-stage transpedicular debridement and fusion for the treatment of thoracolumbar spinal tuberculosis in adults. METHODS: Sixty-six cases of thoracolumbar tuberculosis were treated by single-stage transpedicular debridement, bone graft fusion, and pedicle screw fixation. Thirty-five cases were under long-segment fixation (group A) and 31 cases were under short-segment fixation (group B). These patients were followed up for a minimum of five years. The clinical and radiographic results for these patients were analyzed and compared. RESULTS: All 66 patients were completely cured during the follow-up. All patients had significant improvement of neurological condition and visual analogue scale pain scores at the final follow-up. The average operation duration and blood loss in group A were more than that in group B. Kyphosis Cobb angle of both groups was significantly corrected after surgical management. The correction rate of Cobb angle in group A was significantly higher than that in group B at the time of immediate post-operative period or the last follow-up (P < 0.05). The correction loss of group A was significantly less than that in group B (P < 0.05). CONCLUSION: Both posterior long-segment and short-segment pedicle screw fixations for the treatment of thoracolumbar spinal tuberculosis have significant effects in the correction of kyphosis and the improvement of neurological function. Although the blood loss and operation time of long-segment fixation were more than that of short-segment fixation, long-segment fixation was superior to the short-segment fixation in the correction of kyphosis and the maintenance of spinal stability, especially in the prevention of long-term correction loss.

Self-Assembled Aptamer-Grafted Hyperbranched Polymer Nanocarrier for Targeted and Photoresponsive Drug Delivery.

Photoresponsive materials are emerging as ideal carriers for precisely controlled drug delivery owing to their high spatiotemporal selectivity. However, drawbacks such as slow release kinetics, inherent toxicity, and lack of targeting ability hinder their translation into clinical use. We constructed a new DNA aptamer-grafted photoresponsive hyperbranched polymer, which can self-assemble into nanoparticles, thereby achieving biocompatibility and target specificity, as well as light-controllable release behavior. Upon UV-irradiation, rapid release induced by disassembly was observed for Nile Red-loaded nanoparticles. Further in vitro cell studies confirmed this delivery system's specific binding and internalization performance arising from the DNA aptamer corona. The DOX-loaded nanoassembly exhibited selective phototriggered cytotoxicity towards cancer cells, indicating its promising therapeutic effect as a smart drug delivery system.