Self-Regenerating Photothermal Agents for Tandem Photothermal and Thermodynamic Tumor Therapy.

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS•+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS•+, thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS•+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy.

Bioinspired molecule-functionalized Cu with high CO adsorption for efficient CO electroreduction to acetate.

Electrochemical reduction of carbon dioxide (CO2) or carbon monoxide (CO) to valuable multi-carbon (C2+) products like acetate is a promising approach for a sustainable energy economy. However, it is still challenging to achieve high activity and selectivity for acetate production, especially in neutral electrolytes. Herein, a bioinspired hemin/Cu hybrid catalyst was developed to enhance the surface *CO coverage for highly efficient electroreduction of CO to acetate fuels. The hemin/Cu electrocatalyst exhibits a remarkable faradaic efficiency of 45.2% for CO-to-acetate electroreduction and a high acetate partial current density of 152.3 mA cm-2. Furthermore, the developed hybrid catalyst can operate stably at 200 mA cm-2 for 14.6 hours, producing concentrated acetate aqueous solutions (0.235 M, 2.1 wt%). The results of in situ Raman spectroscopy and theoretical calculations proved that the Fe-N4 structure of hemin could enhance the CO adsorption and enrich the local concentration of CO, thereby improving C-C coupling for acetate production. In addition, compared to the unmodified Cu catalysts, the Cu catalysts functionalized with cobalt phthalocyanine with a Co-N4 structure also exhibit improved acetate performance, proving the universality of this bioinspired molecule-enhanced strategy. This work paves a new way to designing bioinspired electrolysis systems for producing specific C2+ products from CO2 or CO electroreduction.

A photoactivatable upconverting nanodevice boosts the lysosomal escape of PROTAC degraders for enhanced combination therapy.

PROteolysis TArgeting Chimeras have received increasing attention due to their capability to induce potent degradation of various disease-related proteins. However, the effective and controlled cytosolic delivery of current small-molecule PROTACs remains a challenge, primarily due to their intrinsic shortcomings, including unfavorable solubility, poor cell permeability, and limited spatiotemporal precision. Here, we develop a near-infrared light-controlled PROTAC delivery device (abbreviated as USDPR) that allows the efficient photoactivation of PROTAC function to achieve enhanced protein degradation. The nanodevice is constructed by encapsulating the commercial BRD4-targeting PROTACs (dBET6) in the hollow cavity of mesoporous silica-coated upconversion nanoparticles, followed by coating a Rose Bengal (RB) photosensitizer conjugated poly-L-lysine (PLL-RB). This composition enables NIR light-activatable generation of cytotoxic reactive oxygen species due to the energy transfer from the UCNPs to PLL-RB, which boosts the endo/lysosomal escape and subsequent cytosolic release of dBET6. We demonstrate that USDPR is capable of effectively degrading BRD4 in a NIR light-controlled manner. This in combination with NIR light-triggered photodynamic therapy enables an enhanced antitumor effect both in vitro and in vivo. This work thus presents a versatile strategy for controlled release of PROTACs and codelivery with photosensitizers using an NIR-responsive nanodevice, providing important insight into the design of effective PROTAC-based combination therapy.

Operando Spectroscopic Elucidation of the Bubble Sunshade Effect in Inorganic-Biological Hybrids for Photosynthetic Hydrogen Production.

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

Machine Learning for Polymer Design to Enhance Pervaporation-Based Organic Recovery.

Pervaporation (PV) is an effective membrane separation process for organic dehydration, recovery, and upgrading. However, it is crucial to improve membrane materials beyond the current permeability-selectivity trade-off. In this research, we introduce machine learning (ML) models to identify high-potential polymers, greatly improving the efficiency and reducing cost compared to conventional trial-and-error approach. We utilized the largest PV data set to date and incorporated polymer fingerprints and features, including membrane structure, operating conditions, and solute properties. Dimensionality reduction, missing data treatment, seed randomness, and data leakage management were employed to ensure model robustness. The optimized LightGBM models achieved RMSE of 0.447 and 0.360 for separation factor and total flux, respectively (logarithmic scale). Screening approximately 1 million hypothetical polymers with ML models resulted in identifying polymers with a predicted permeation separation index >30 and synthetic accessibility score <3.7 for acetic acid extraction. This study demonstrates the promise of ML to accelerate tailored membrane designs.

DNA Walker-Driven Mass Nanotag Assembly System for Simultaneously Profiling Dual Markers of Oxidative Stress at Different Cellular Locations.

Simultaneous profiling of redox-regulated markers at different cellular sublocations is of great significance for unraveling the upstream and downstream molecular mechanisms of oxidative stress in living cells. Herein, by synchronizing dual target-triggered DNA machineries in one nanoentity, we engineered a DNA walker-driven mass nanotag (MNT) assembly system (w-MNT-AS) that can be sequentially activated by oxidative stress-associated mucin 1 (MUC1) and apurinic/apyrimidinic endonuclease 1 (APE1) from plasma membrane to cytoplasm and induce recycled assembly of MNTs for multiplex detection of the two markers by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). In the working cascade, the sensing process governs the separate activation of w-MNT-AS by MUC1 and APE1 in diverse locations, while the assembly process contributes to the parallel amplification of the ion signal of the characteristic mass tags. In this manner, the differences between MCF-7, HeLa, HepG2, and L02 cells in membrane MUC1 expression and cytoplasmic APE1 activation were fully characterized. Furthermore, the oxidative stress level and dynamics caused by exogenous H2O2, doxorubicin, and simvastatin were comprehensively demonstrated by tracking the fate of the two markers across different cellular locations. The proposed w-MNT-AS coupled MS method provides an effective route to probe multiple functional molecules that lie at different locations while participating in the same cellular event, facilitating the mechanistic studies on cellular response to oxidative stress and other disease-related cellular processes.

Versatile Metal-Organic Framework Incorporating Ag2S for Constructing a Photoelectrochemical Immunosensor for Two Breast Cancer Markers.

Breast cancer poses the significance of early diagnosis and treatment. Here, we developed an innovative photoelectrochemical (PEC) immunosensor characterized by high-level dual photocurrent signals and exceptional sensitivity. The PEC sensor, denoted as MIL&Ag2S, was constructed by incorporating Ag2S into a metal-organic framework of MIL-101(Cr). This composite not only enhanced electron-hole separation and conductivity but also yielded robust and stable dual photocurrent signals. Through the implementation of signal switching, we achieved the combined detection of cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) with outstanding stability, reproducibility, and specificity. The results revealed a linear range for CEA detection spanning 0.01-32 ng/mL, with a remarkably low detection limit of 0.0023 ng/mL. Similarly, for CA15-3 detection, the linear range extended from 0.1 to 320 U/mL, with a low detection limit of 0.014 U/mL. The proposed strategy introduces new avenues for the development of highly efficient, cost-effective, and user-friendly PEC sensors. Furthermore, it holds promising prospects for early clinical diagnosis, contributing to potential breakthroughs in medical detection and ultimately improving patient outcomes.

High Dynamic Range Probing of Single-Molecule Mechanical Force Transitions at Cell-Matrix Adhesion Bonds by a Plasmonic Tension Nanosensor.

Mechanical signals in animal tissues are complex and rapidly changed, and how the force transduction emerges from the single-cell adhesion bonds remains unclear. DNA-based molecular tension sensors (MTS), albeit successful in cellular force probing, were restricted by their detection range and temporal resolution. Here, we introduced a plasmonic tension nanosensor (PTNS) to make straight progress toward these shortcomings. Contrary to the fluorescence-based MTS that only has specific force response thresholds, PTNS enabled the continuous and reversible force measurement from 1.1 to 48 pN with millisecond temporal resolution. We used the PTNS to visualize the high dynamic range single-molecule force transitions at cell-matrix adhesions during adhesion formation and migration. Time-resolved force traces revealed that the lifetime and duration of stepwise force transitions of molecular clutches are strongly modulated by the traction force through filamentous actin. The force probing technique is sensitive, fast, and robust and constitutes a potential tool for single-molecule and single-cell biophysics.

Ring-Contracted Artemisinin Derivatives as Novel CDK 4/6 Inhibitors: Synthesis and Anti-Breast Cancer Evaluation.

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Prolonged near-infrared fluorescence imaging of microRNAs and proteases in vivo by aggregation-enhanced emission from DNA-AuNC nanomachines.

Developing a comprehensive strategy for imaging various biomarkers (i.e., microRNAs and proteases) in vivo is an exceptionally formidable task. Herein, we have designed a deoxyribonucleic acid-gold nanocluster (DNA-AuNC) nanomachine for detecting tumor-related TK1 mRNA and cathepsin B in living cells and in vivo. The DNA-AuNC nanomachine is constructed using AuNCs and DNA modules that incorporate a three component DNA hybrid (TD) and a single-stranded fuel DNA (FD). Upon being internalized into tumor cells, the TK1 mRNA initiates the DNA-AuNC nanomachine through DNA strand displacement cascades, leading to the amplified self-assembly and the aggregation-enhanced emission of AuNCs for in situ imaging. Furthermore, with the aid of a protease nanomediator consisting of a mediator DNA/peptide complex and AuNCs (DpAuNCs), the DNA-AuNC nanomachine can be triggered by the protease-activated disassembly of the DNA/peptide complex on the nanomediator, resulting in the aggregation of AuNCs for in vivo protease amplified detection. It is worth noting that our study demonstrates the impressive tumor permeability and accumulation capabilities of the DNA-AuNC nanomachines via in situ amplified self-assembly, thereby facilitating prolonged imaging of TK1 mRNA and cathepsin B both in vitro and in vivo. This strategy presents a versatile and biomarker-specific paradigm for disease diagnosis.

Quantifying source contributions to ambient NH3 using Geo-AI with time lag and parcel tracking functions.

Ambient ammonia (NH3) plays an important compound in forming particulate matters (PMs), and therefore, it is crucial to comprehend NH3's properties in order to better reduce PMs. However, it is not easy to achieve this goal due to the limited range/real-time NH3 data monitored by the air quality stations. While there were other studies to predict NH3 and its source apportionment, this manuscript provides a novel method (i.e., GEO-AI)) to look into NH3 predictions and their contribution sources. This study represents a pioneering effort in the application of a novel geospatial-artificial intelligence (Geo-AI) base model with parcel tracking functions. This innovative approach seamlessly integrates various machine learning algorithms and geographic predictor variables to estimate NH3 concentrations, marking the first instance of such a comprehensive methodology. The Shapley additive explanation (SHAP) was used to further analyze source contribution of NH3 with domain knowledge. From 2016 to 2018, Taichung's hourly average NH3 values were predicted with total variance up to 96%. SHAP values revealed that waterbody, traffic and agriculture emissions were the most significant factors to affect NH3 concentrations in Taichung among all the characteristics. Our methodology is a vital first step for shaping future policies and regulations and is adaptable to regions with limited monitoring sites.

Lipid concentration and composition in xylem sap of woody angiosperms from a tropical savanna and a seasonal rainforest.

Lipids may play an important role in preventing gas embolisms by coating nanobubbles in xylem sap. Few studies on xylem sap lipids have been reported for temperate plants, and it remain unclear whether sap lipids have adaptational significance in tropical plants. In this study, we quantify the lipid composition of xylem sap for angiosperm species from a tropical savanna (seven species) and a seasonal rainforest (five species) using mass spectrometry. We found that all twelve species studied contained lipids in their xylem sap, including galactolipids, phospholipids and triacylglycerol, with a total lipid concentration ranging from 0.09 to 0.26 nmol/L. There was no difference in lipid concentration or composition between plants from the two sites, and the lipid concentration was negatively related to species' open vessel volume. Furthermore, savanna species showed little variation in lipid composition between the dry and the rainy season. These results support the hypothesis that xylem sap lipids are derived from the cytoplasm of individual conduit cells, remain trapped inside individual conduits, and undergo few changes in composition over consecutive seasons. A xylem sap lipidomic data set, which includes 12 tropical tree species from this study and 11 temperate tree species from literature, revealed no phylogenetic signals in lipid composition for these species. This study fills a knowledge gap in the lipid content of xylem sap in tropical trees and provides additional support for their common distribution in xylem sap of woody angiosperms. It appears that xylem sap lipids have no adaptive significance.

Unraveling assemblage of microbial community dwelling in Dabaoshan As/Pb/Zn mine-impacted area: A typical mountain mining area of South China.

Microbial community assemblage includes microorganisms from the three domains including Bacteria, Archaea, and Eukarya (Fungi), which play a crucial role in geochemical cycles of metal(loid)s in mine tailings. Mine tailings harbor vast proportions of metal(loid)s, representing a unique source of co-contamination of metal(loid)s that threaten the environment. The elucidation of the assembly patterns of microbial communities in mining-impacted ecospheres has received little attention. To decipher the microbial community assembly processes, the microbial communities from the five sites of the Dabaoshan mine-impacted area were profiled by the MiSeq sequencing of 16S rRNA (Bacteria and Archaea) genes and internal transcribed spacers (Fungi). Results indicated that the coexistence of 31 bacterial, 10 fungal, and 3 archaeal phyla, were mainly dominated by Mucilaginibacter, Cladophialophora, and Candidatus Nitrosotalea, respectively. The distribution of microorganisms was controlled by deterministic processes. The combination of Cu, Pb, and Sb was the main factor explaining the structure of microbial communities. Functional predicting analysis of bacteria and archaea based on the phylogenetic investigation of communities by reconstruction of unobserved states analyses revealed that the metabolic pathways related to arsenite transporter, arsenate reductase, and FeS cluster were important for metal detoxification. Furthermore, the ecological guilds (pathogens, symbiotrophs, and saprotrophs) of fungal communities explained 44.5 % of functional prediction. In addition, metal-induced oxidative stress may be alleviated by antioxidant enzymes of fungi communities, such as catalase. Such information provides new insights into the microbial assembly rules in co-contaminated sites.

Aggregation-Induced Enhanced Electrochemiluminescence from Tris(bipyridine)ruthenium(II) Derivative Nanosheets for the Ultrasensitive Detection of Human Telomerase RNA.

The traditional tris(bipyridine)ruthenium(II) complex suffers from the notorious aggregation-caused quenching effect, which greatly compromises its electrochemiluminescence (ECL) efficiency, thus hindering further applications in biosensing and clinical diagnosis. Here, the ultrathin tetraphenylethylene-active tris(bipyridine)ruthenium(II) derivative nanosheets (abbreviated as Ru-TPE NSs) are synthesized through a protein-assisted self-assembly strategy for ultrasensitive ECL detection of human telomerase RNA (hTR) for the first time. The synthesized Ru-TPE NSs exhibit the aggregation-induced enhanced ECL behavior and excellent water-dispersion. Surprisingly, up to a 106.5-fold increase in the ECL efficiency of Ru-TPE NSs is demonstrated compared with the dispersed molecules in an organic solution. The restriction of intramolecular motions is confirmed to be responsible for the significant ECL enhancement. Therefore, this proposed ECL biosensor shows high sensitivity and excellent selectivity for hTR based on Ru-TPE NSs as efficient ECL beacons and the catalytic hairpin assembly as signal amplification, whose detection limit is as low as 8.0 fm, which is far superior to the previously reported works. Here, a promising analytical method is provided for early clinical diagnosis and a new type of efficient ECL emitters with great application prospects is represented.

Quality Control of Mass-Encoded Nanodevices by Compartmented DNA Origami Frames for Precision Information Coding and Logic Mapping.

Encoded nanostructures afford an ideal platform carrying multi-channel signal components for multiplexed assay and information security. However, with the demand on exclusivity and reproducibility of coding signals, precise control on the structure and composition of nanomaterials featuring fully distinguishable signals remains challenging. By using the multiplexing capability of mass spectrometry (MS) and spatial addressability of DNA origami nanostructures, we herein propose a quality control methodology for constructing mass-encoded nanodevices (namely MNTs-TDOFs) in the scaffold of compartmented tetrahedral DNA origami frames (TDOFs), in which the arrangement and stoichiometry of four types of mass nanotags (MNTs) can be finely regulated and customized to generate characteristic MS patterns. The programmability of combinatorial MNTs and orthogonality of individual compartments allows further evolution of MNTs-TDOFs to static tagging agents and dynamic nanoprobes for labeling and sensing of multiple targets. More importantly, structure control at single TDOF level ensures the constancy of prescribed MS outputs, by which a high-capacity coding system was established for secure information encryption and decryption. In addition to the multiplexed outputs in parallel, the nanodevices could also map logic circuits with interconnected complexity and logic events of c-Met recognition and dimerization on cell surface for signaling regulation by MS interrogation.

Cu-based catalyst designs in CO2 electroreduction: precise modulation of reaction intermediates for high-value chemical generation.

The massive emission of excess greenhouse gases (mainly CO2) have an irreversible impact on the Earth's ecology. Electrocatalytic CO2 reduction (ECR), a technique that utilizes renewable energy sources to create highly reduced chemicals (e.g. C2H4, C2H5OH), has attracted significant attention in the science community. Cu-based catalysts have emerged as promising candidates for ECR, particularly in producing multi-carbon products that hold substantial value in modern industries. The formation of multi-carbon products involves a range of transient intermediates, the behaviour of which critically influences the reaction pathway and product distribution. Consequently, achieving desirable products necessitates precise regulation of these intermediates. This review explores state-of-the-art designs of Cu-based catalysts, classified into three categories based on the different prospects of the intermediates' modulation: heteroatom doping, morphological structure engineering, and local catalytic environment engineering. These catalyst designs enable efficient multi-carbon generation in ECR by effectively modulating reaction intermediates.

Molecular detection of Bartonella species in wild small mammals in western Yunnan Province, China.

Background: Small mammals serve as the main reservoir for Bartonella and as a proxy indicator of the potential risk of Bartonella transmission from nature to humans. They offer a valuable early warning for human infection. Nevertheless, geographical variations in the impact of the host on the occurrence of Bartonella infection are underestimated. This study was designed to investigate the infection characteristics of Bartonella and explore its species diversity in wild small mammals in western Yunnan Province, China. Methods: Wild small mammals were captured from Yulong, Jianchuan, and Lianghe counties in western Yunnan Province between 2015 and 2016. Real-time quantitative PCR (qPCR) was used to detect Bartonella infection, and the Bartonella species were identified by phylogenetic analysis. The factors associated with Bartonella infection in small mammals were analyzed by the Chi-square Test. Results: The prevalence of Bartonella in small mammals was 47.85% (768/1605). Lianghe County had the highest Bartonella infection rate, with 56.27% of the samples tested positive, followed by a rate of 50.91% was tested in Yulong County, and 39.97% in Jianchuan County (p < 0.001). Bartonella was detected positive in a total 25 small mammal species, with infection rates ranging from 2.17% to 100%. Niviventer fulvescens had the highest Bartonella infection rate. In comparison with the dominant small mammal species, Eothenomys mileyus had the lowest Bartonella infection rate than that in Apodemus chevrieri, Rattus tanezumi, and Apodemus draco (p < 0.001). Male small mammals had a higher infection rate than females (p < 0.05). The prevalence of Bartonella in small mammals during the summer season was higher compared to the other three seasons (p < 0.001). Woodland landscape had the highest Bartonella infection rate (p < 0.001). Bartonella rochalimae, B. japonica, B. tribocorum, B. washoensis, B. sylvatica, and B. rattimassiliensis were obtained from infected small mammals. Conclusion: This study showed a high prevalence of Bartonella was detected with various Bartonella species in small mammals in Yulong, Jianchuan, and Lianghe counties of western Yunnan Province. These findings hold significant scientific clues, providing valuable reference points for further research of Bartonella natural foci in Yunnan or other analogues environments.

Confinement in Dual-Chain-Locked DNA Origami Nanocages Programs Marker-Responsive Delivery of CRISPR/Cas9 Ribonucleoproteins.

Delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) offers a powerful tool for therapeutic genome editing. However, precise manipulation of CRISPR/Cas9 RNPs to switch the machinery on and off according to diverse disease microenvironments remains challenging. Here, we present dual-chain-locked DNA origami nanocages (DL-DONCs) that can confine Cas9 RNPs in the inner cavity for efficient cargo delivery and dual-marker-responsive genome editing in the specified pathological states. By engineering of ATP or miRNA-21-responsive dsDNAs as chain locks on the DONCs, the permeability of nanocages and accessibility of encapsulated Cas9 RNPs can be finely regulated. The resulting DL-DONCs enabled steric protection of bioactive Cas9 RNPs from premature release and deactivation during transportation while dismounting the dual chain locks in response to molecular triggers after internalization into tumor cells, facilitating the escape of Cas9 RNPs from the confinement for gene editing. Due to the dual-marker-dominated uncaging mechanism, the gene editing efficiency could be exclusively determined by the combined level of ATP and miRNA-21 in the target cellular environment. By targeting the tumor-associated PLK-1 gene, the DL-DONCs-enveloped Cas9 RNPs have demonstrated superior inhibitory effects on the proliferation of tumor cells in vitro and in vivo. The developed DL-DONCs provide a custom-made platform for the precise manipulation of Cas9 RNPs, which can be potentially applied to on-demand gene editing for classified therapy in response to arbitrary disease-associated biomolecules.

Cell-Derived N/P/S-Codoped Fluorescent Carbon Nanodots with Intrinsic Targeting Ability for Tumor-Specific Phototheranostics.

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200-900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (1O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal-photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.