Rapid Determination of Cr3+ and Mn2+ in Water Using Laser-Induced Breakdown Spectroscopy Combined with Filter Paper Modified with Gold Nanoclusters.

Excessive emissions of heavy metals not only cause environmental pollution but also pose a direct threat to human health. Therefore, rapid and accurate detection of heavy metals in the environment is of great significance. Herein, we propose a method based on laser-induced breakdown spectroscopy (LIBS) combined with filter paper modified with bovine serum albumin-protected gold nanoclusters (LIBS-FP-AuNCs) for the rapid and sensitive detection of Cr3+ and Mn2+. The filter paper modified with AuNCs was used to selectively enrich Cr3+ and Mn2+. Combined with the multi-element detection capability of LIBS, this method achieved the simultaneous rapid detection of Cr3+ and Mn2+. Both elements showed linear ranges for concentrations of 10-1000 µg L-1, with limits of detection of 7.5 and 9.0 µg L-1 for Cr3+ and Mn2+, respectively. This method was successfully applied to the determination of Cr3+ and Mn2+ in real water samples, with satisfactory recoveries ranging from 94.6% to 105.1%. This method has potential application in the analysis of heavy metal pollution.

Gold nanoclusters-based fluorescence sensor array for herbicides qualitative and quantitative analysis.

Herbicides have been extensively used around the world, which poses a potential hazard to humans and wildlife. Accurate detection of herbicides is crucial for the environment and human health. Herein, a simple and sensitive fluorescence sensor array was constructed for discrimination and identification of herbicides. Fluorescent gold nanoclusters modified with 11-mercaptoundecanoic acid or reduced glutathione were prepared, respectively. Metal ions quenched the fluorescence of nanoclusters through coordination and leading to the aggregation of gold nanoclusters. The addition of auxin herbicides (2,4-dichlorophenoxyacetic acid, 2-methyl-4-chlorophenoxyacetic acid, decamba, picloram, quinclorac) restored the fluorescence of nanoclusters with different degrees. The mechanism study showed auxin herbicides can bind with metal ions and re-disperse the gold nanoclusters from the aggregation state. The "on-off-on" fluorescent sensor array was constructed basic on above detection mechanism. Combined with principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods, auxin herbicides are well separated on 2D/3D PCA score plots and HCA dendrogram in the range of 40-500 µm. In addition, the fluorescence sensor array performed successful in detecting real samples and blind samples. The developed sensor system shows a promising in practical detection of herbicides.

Bimetallic Ag/Au nanoclusters encapsulated in ZIF-8 framework: A novel strategy for ratiometric fluorescence detection of doxycycline in food.

This study successfully encapsulated the Ag+-doped Au nanoclusters (Ag/AuNCs) within the ZIF-8 framework to construct a novel Ag/AuNCs@ZIF-8 ratiometric fluorescent probe for the antibiotic doxycycline (DOX) detection. The incorporation of Ag+ contributed to the fluorescence enhancement of the nanoclusters through the "silver effect", consequently improving the stability of the developed bimetallic Ag/AuNCs. Furthermore, the encapsulation of bimetallic Ag/AuNCs within the ZIF-8 framework restricted their intramolecular vibrations, resulting in further amplification of fluorescence intensity at 595 nm. The ZIF-8 also sensitized the restoration of DOX green fluorescence at 515 nm. Within the concentration range of 0.001-20 µg mL-1, the ratio of fluorescence intensity (F515/F595) exhibited a favorable linearity for DOX concentration, with a detection limit of 36.8 ng mL-1. This ratiometric fluorescence approach had the promising potential for accurate and efficient quantitative detection of DOX residue in food and served as a valuable reference for rapid monitoring of food contaminants.

Advanced Functionalized Nanoclusters (Cu, Ag, and Au) as Effective Catalyst for Organic Transformation Reactions.

A considerable amount of research has been carried out in recent years on synthesizing metal nanoclusters (NCs), which have wide applications in the field of optical materials with non-linear properties, bio-sensing, and catalysis. Aside from being structurally accurate, the atomically precise NCs possess well-defined compositions due to significant tailoring, both at the surface and the core, for certain functionalities. To illustrate the importance of atomically precise metal NCs for catalytic processes, this review emphasizes 1) the recent work on Cu, Ag, and Au NCs with their synthesis, 2) the parameters affecting the activity and selectivity of NCs catalysis, and 3) the discussion on the catalytic potential of these metal NCs. Additionally, metal NCs will facilitate the design of extremely active and selective catalysts for significant reactions by elucidating catalytic mechanisms at the atomic and molecular levels. Future advancements in the science of catalysis are expected to come from the potential to design NCs catalysts at the atomic level.

Synthesis and Application of a Near-Infrared Light-Emitting Fluorescent Probe for Specific Imaging of Cancer Cells with High Sensitivity and Selectivity.

Background: The preclinical diagnosis of tumors is of great significance to cancer treatment. Near-infrared fluorescence imaging technology is promising for the in-situ detection of tumors with high sensitivity. Methods: Here, a fluorescent probe was synthesized on the basis of Au nanoclusters with near-infrared light emission and applied to fluorescent cancer cell labeling. Near-infrared methionine-N-Hydroxy succinimide Au nanoclusters (Met-NHs-AuNCs) were prepared successfully by one-pot synthesis using Au nanoclusters, methionine, and N-Hydroxy succinimide as frameworks, reductants, and stabilizers, respectively. The specific fluorescence imaging of tumor cells or tissues by fluorescent probe was studied on the basis of SYBYL Surflex-DOCK simulation model of LAT1 active site of overexpressed receptor on cancer cell surface. The results showed that Met-NHs-AuNCs interacted with the surface of LAT1, and C_Score scored the conformation of the probe and LAT1 as five. Results: Characterization and in vitro experiments were conducted to explore the Met-NHs-AuNCs targeted uptake of cancer cells. The prepared near-infrared fluorescent probe (Met-NHs-AuNCs) can specifically recognize the overexpression of L-type amino acid transporter 1 (LAT1) in cancer cells so that it can show red fluorescence in cancer cells. Meanwhile, normal cells (H9c2) have no fluorescence. Conclusion: The fluorescent probe demonstrates the power of targeting and imaging cancer cells.

Metasurface Absorbers with Film-Coupled Au Nanoclusters to Achieve Broadband and Polarization-Independent Absorption of UV-Vis Light.

Metasurface absorbers (MAs) have attracted widespread interest in the recent study of subwavelength artificial optical metasurfaces, although most reported MAs suffer from the actualities of costly and time-consuming fabrications, narrow working bandwidth, polarization-dependent responses, etc., somewhat limiting their practical applications. Herein, we introduce a facile and low-cost method to fabricate MAs with excellent absorption performances via the self-assembly of synthesized Au nanoclusters (NCs) on a Au film spaced by a nanoscale-thick dielectric SiO2. Interestingly, the proposed MAs with well-designed Au film-coupled Au NCs (i.e., an appropriate surface coverage of Au NCs and the compatible thickness of the SiO2 spacer) exhibited a measured average absorbance above 90% within a broad UV-vis wavelength band (200-800 nm). In addition, owing to the MAs' topological symmetry, their UV-vis absorption behaviors presented polarization insensitivity with the incident light angles ranging from 20 to 50°. It has been demonstrated that the excited different surface plasmon resonance modes between Au NCs and the adjacent Au film were vital; in addition, the light-trapping effects from "V"-shaped structures of Au NCs were favorable for the designed MAs with enhanced light absorption. We believe that such MAs and the potential self-assembly fabrication strategy may facilitate scalable optical applications such as photothermalvoltaics, ultraviolet protection, optical storage, and sensing.

Ultrafast Subcellular Biolabeling and Bioresponsive Real-Time Monitoring for Targeting Cancer Theranostics.

Cell heterogeneity poses a formidable challenge for tumor theranostics, requiring high-resolution strategies for intercellular bioanalysis between single cells. Nanoelectrode-based electrochemical analysis has attracted much attention due to its advantages of label-free characteristics, relatively low cost, and ultra-high resolution for single-cell analysis. Here, we have designed and developed a subcellular biolabeling and bioresponsive real-time monitoring strategy for precise bioimaging-guided cancer diagnosis and theranostics. Our observations revealed the apparent intracellular migration of biosynthetic Au nanoclusters (Au NCs) at different subcellular locations, i.e., from the mitochondria to the mitochondrion-free region in the cytoplasm, which may be helpful for controlling over the biosynthesis of Au NCs. Considering the precise biolabeling advantage of the intracellular biosynthetic Au NCs for biomedical imaging of cancers, it is important to realize the biosynthetic Au NC-enabled precise control in real-time theranostics of cancer cells. Therefore, this work raises the possibility to achieve subcellular monitoring of H2O2 for targeting cancer theranostics, thereby providing a new way to explore the underlying mechanism and imaging-guided tumor theranostics.

Dual-functional cellulase-mediated gold nanoclusters for ascorbic acid detection and fluorescence bacterial imaging.

Protein-protected metal nanomaterials are becoming the most promising fluorescent nanomaterials for biosensing, bioimaging, and therapeutic applications due to their obvious fluorescent molecular properties, favorable biocompatibility and excellent physicochemical properties. Herein, we pioneeringly prepared a cellulase protected fluorescent gold nanoclusters (Cel-Au NCs) exhibiting red fluorescence under the excitation wavelength of 560 nm via a facile and green one-step method. Based on the fluorescence turn-off mechanism, the Cel-Au NCs were used as a biosensor for specificity determination of ascorbic acid (AA) at the emission of 680 nm, which exhibited satisfactory linearity over the range of 10-400 µM and the detection limit of 2.5 µM. Further, the actual sample application of the Au NCs was successfully established by evaluating AA in serum with good recoveries of 98.76%-104.83%. Additionally, the bacteria, including gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), were obviously stained by Cel-Au NCs with strong red emission. Thereby, as dual-functional nanoclusters, the prepared Cel-Au NCs have been proven to be an excellent fluorescent bioprobe for the detection of AA and bacterial labeling in medical diagnosis and human health maintenance.

Size transformation of Au nanoclusters for enhanced photocatalytic hydrogen generation: Interaction behavior at nanocluster/semiconductor interface.

Recently, atomically precise metal nanoclusters (NCs) become a new class of photosensitizer for light energy conversion in metal-cluster-sensitized semiconductor (MCSS) system. However, fundamental understanding for the suitable combination of NCs and semiconductor is still unclear. Aside from aspects of light harvesting, energy level alignment and catalytic activity, interfacial interaction behavior at NCs/semiconductor interface is also crucial due to its important influence in charge transportation. In this work, the interface interaction between Au NCs and TiO2 is examined by precise transformation of Au NCs from Au22(SG)18 to Au18(SG)14, as well as its effect on photocatalytic hydrogen production activity. From the optical, charge transport and solid-states spectroscopy analyses, it is able to display that precisely tuning the number of core atoms from Au22(SG)18 to Au18(SG)14 results in the strong interface interaction between Au NCs and TiO2, reflecting in high difference of work function and modified surface band bending of TiO2, therefore promoting the injection of electrons from NCs to TiO2 and reducing interfacial charges recombination. As a result, Au18(SG)14/TiO2 shows higher hydrogen generation rate than Au22(SG)18/TiO2 under light irradiation. This work would provide new insights into rational combination of metal NCs with semiconductor and highlights the overlooked effect of interfacial interaction behavior on light energy conversion.

Electron Injection via Interfacial Atomic Au Clusters Substantially Enhance the Visible-Light-Driven Photocatalytic H2 Production of the PF3T Enclosed TiO2 Nanocomposite.

A hybrid composite of organic-inorganic semiconductor nanomaterials with atomic Au clusters at the interface decoration (denoted as PF3T@Au-TiO2 ) is developed for visible-light-driven H2 production via direct water splitting. With a strong electron coupling between the terthiophene groups, Au atoms and the oxygen atoms at the heterogeneous interface, significant electron injection from the PF3T to TiO2 occurs leading to a quantum leap in the H2 production yield (18 578 µmol g-1 h-1 ) by ≈39% as compared to that of the composite without Au decoration (PF3T@TiO2 , 11 321 µmol g-1 h-1 ). Compared to the pure PF3T, such a result is 43-fold improved and is the best performance among all the existing hybrid materials in similar configurations. With robust process control via industrially applicable methods, it is anticipated that the findings and proposed methodologies can accelerate the development of high-performance eco-friendly photocatalytic hydrogen production technologies.

The synthesis of gold nanoclusters with high stability and their application in fluorometric detection for Hg2+ and cell imaging.

Sensing Hg2+ is significant to protecting human health and environmental ecosystems, for its toxicity and genotoxicity. Here, highly stable fluorescent folic acid (FA)-protected Au nanoclusters (FA-AuNCs) were synthesized by optimizing the reactive parameters with high quantum yield of 34.7%. Main components of Au4L were confirmed by MALDI-TOF, and the electron-rich residues of FA shell enabled FA-AuNCs excellent photostability. FA-AuNCs exhibited sensitive response behavior to Hg2+ with a minimum detectability of 1.3 nM, and presented extreme effect to the detection of Hg2+ in real water. Notably, the cellular imaging and in-situ detection of Hg2+ in cells can be achieved visually. The high selectivity was attributed to the chemical bond formed between Au+ (4f145d10) and Hg2+ (4f145d10). And the internal filter effect and static quenching effect were proved triggering the quenching of FA-AuNCs. The ultra-stable FA-AuNCs provide a potential promising opportunity for the in-situ tracing Hg2+ from environmental and biological samples.

Gold nanoclusters with enhanced near-infrared emission and its application as sensors for biological molecules.

Ultrasmall gold nanoclusters (NCs) have been engineered as a new kind of functional material due to their excellent photoluminescence properties. However, the synthesis of highly luminescent water-soluble nanoclusters with near-infrared (NIR) emission remains limited. Herein, we developed a pH-regulated strategy to facilitate the construction of self-assemblies with enhanced luminescence based on aggregation-induced emission (AIE) strategy. Using 2-mercaptobenzoic acid (MBA) as reductant and stabilizer, the original weakly luminescent AuNCs exhibited intense emission by adjusting pH controllably. The formation of compact organized nanostructures could effectively restrict the rotation and vibration of capping ligands by non-covalent interactions, which reduced the nonradiative relaxation from excited states and finally improved the emission properties of AuNCs. Moreover, the assemblies possess many intriguing features including bright NIR luminescence and excellent biocompatibility, which could be used as luminous probes in biological molecules sensing (tyrosinase (TYR) and dopamine (DA)) and promising candidates for cell imaging. This study provides a simple and feasible strategy for developing metal NCs-based smart optical materials in the field of bioscience.

Design of a novel aptamer/molecularly imprinted polymer hybrid modified Ag-Au@Insulin nanoclusters/Au-gate-based MoS2 nanosheet field-effect transistor for attomolar detection of BRCA1 gene.

Early detection of breast cancer, the first main cause of death in women, with robust assay platforms using appropriate biomarkers is of great importance for diagnosis and follow-up of the disease progression. This paper introduces an extra selective and sensitive label-free aptasensor for the screening of BRCA1 gene biomarker by taking advantage of a gate modified with aptamer and molecularly imprinted polymer hybrid (MIP) as a new synthetic receptor film coupled with an electrolyte-gated molybdenum disulfide (MoS2) field-effect transistor (FET). The Au gate surface of FET was modified with insulin stabilized bimetallic Ag-Au@nanoclusters (Ag-Au@InsNCs), after which, the immobilization of the hybridized aptamer and o-phenylenediamine was electropolymerized to form an aptamer-MIP hybrid receptor. The output characteristics of Apta-MIP hybrid modified Au gate MoS2 FET device were followed as a result of change in electrical double layer capacitance of electrolye-gate interface. The magnitude of decrease in the drain current showed a linear response over a wide concentration range of 10 aM to 1 nM of BRCA1 ssDNA with a sensitivity as high as 0.4851 µA/decade of concentration and a limit of detection (LOD) of 3.0 aM while very low responses observed for non-imprinted polymer. The devised aptasensor not only was capable to the discrimination of the complementary versus one-base mismatch BRCA1 ssDNA sequence, but also it could detect the complementary BRCA1 ssDNA in spiked human serum samples over a wide concentration range of 10 aM to 1.0 nM with a low LOD of 6.4 aM and a high sensitivity 0.3718 µA/decade.

Electron Delocalization of Au Nanoclusters Triggered by Fe Single Atoms Boosts Alkaline Overall Water Splitting.

The rational design and in-depth understanding of the structure-activity relationship (SAR) of hydrogen and oxygen evolution reaction (HER and OER) bifunctional electrocatalysts are vital to decreasing the energy consumption of hydrogen production by electrochemical water splitting. Herein, we report an inducing electron delocalization method where Fe single atoms as inducers are used to regulate the electron structure of Au nanoclusters by the M-Nx-C substrate to acquire satisfactory intrinsic HER activity. Meanwhile, Fe single atoms also serve as efficient OER active sites to construct bifunctional electrocatalysts. On account of the strong synergistic effect between Au nanoclusters and Fe single atoms, the hybrid catalyst Au-Fe1NC/NF performs an outstanding alkaline HER and OER activity. Only 35.6 mV, 246 mV, and 1.52 V are needed to reach 10 mA cm-2 for alkaline HER, OER, and two-electrode electrolytic cells, respectively. In addition, the bifunctional electrocatalysts also display excellent electrochemical stability. DFT calculations demonstrate that the strong synergistic effect can enhance the O-H bond activation ability of Au nanoclusters and upshift the d-band center of the Fe single atom to promote alkaline electrocatalytic water splitting. The strong synergistic effect is proven to arise from the electron delocalization of Au nanoclusters triggered by Fe single atoms.

Development of an Au nanoclusters based activatable nanoprobe for NIR-II fluorescence imaging of gastric acid.

Gastric acid is an important functional substance secreted by the stomach of the living organisms, reflecting the gastric physiological condition. The sensing of gastric acid in vivo is of great significance for evaluation of gastric function, diagnosis and treatment of gastric diseases and maintenance of organism health but remains challenging due to the harsh acid and digestive environment of stomach. This study developed an activatable nanoprobe based on Au nanoclusters (Au NCs) for sensitive and real-time noninvasive near-infrared II (NIR-II) fluorescence imaging detection of gastric acid in vivo for the first time. The Au NCs were encapsulated by polydopamine to have enhanced NIR-II luminescence and high stability and combined with methylene blue to possess the pH responsiveness for gastric acid imaging. The developed nanoprobe could not only monitor gastric acid secretion in vivo but also imaging the changes of gastric acid caused by feeding, acid-inhibition drugs and gastric ulcer disease. This study provides a promising avenue for the improvement of the application performance of Au NCs and imaging analysis of gastric acid and related gastric diseases.

Non-enzymatic electrochemiluminescence biosensor for ultrasensitive detection of ochratoxin A based on efficient DNA walker.

Ochratoxin A (OTA) with high toxicity represents a serious threat to the agriculture and food chain, consequently to human health. Herein, a simple electrochemiluminescence (ECL) biosensor was constructed for ultrasensitive detection of OTA based on mercaptopropionic acid templated Au nanoclusters (Au NCs) as intensive signal probe and a non-enzymatic 2D DNA walking machine as the effective amplification strategy. Specifically, the target related bipedal DNA walker efficiently moved along 2D DNA tracks through toehold-mediated DNA strand displacement, which triggered abundant signal probes for combining to the DNA tracks. Moreover, the Au NCs could exhibit strong ECL emission due to fast electron transfer from massive Au-S electronic pathways under the electrochemical excitation. Thus, the biosensor possessed significant ECL response for achieving ultrasensitive detection toward OTA with low detection limit of 3.19 fg/mL. Impressively, the sensing platform was also applied to detect OTA from edible oils, exhibiting great application potential in food analysis.

Ratiometric fluorescence probe integrated with smartphone for visually detecting lipopolysaccharide.

A portable instrument-free detection method for lipopolysaccharide (LPS) analysis was developed based on dual-emission ratiometric fluorescence sensing system. Herein, red-emitting Au nanoclusters (Au NCs) were as reference probe, while blue-emitting fluorescent silica quantum dots (Si QDs) were as response probe. Additionally, the aptamer of LPS was covalently grafted to the surface of Si QDs in order to specific recognize the LPS. According to the changes of fluorescence intensityratio (FL ratio, I461 nm/I643 nm) with the concentrations of LPS, the linear equation was fitted with the range of 50-3000 ng/mL, and the limit of detection (LOD) was 29.3 ng/mL. As a practical application, this method was employed to analyze LPS in normal saline with the recovery rate of 97.7-103.8 %. The color picker platform in the smartphone was used to transform the detection picture to the process of Red, Green and Blue (RGB) for visual detection of LPS. The low-cost and easy-carry method reported here presents broad merits for the visually quantitative detection of LPS.

Cerium ions triggered dual-readout immunoassay based on aggregation induced emission effect and 3,3',5,5'-tetramethylbenzidine for fluorescent and colorimetric detection of ochratoxin A.

Ochratoxin A (OTA) is one of the most prevalent and toxic mycotoxins. Ultrasensitive and convenient detection of OTA is urgent demanded for public health. In this work, a dual-readout immunoassay was established for the detection of OTA based on Ce4+ oxidizing 3,3',5,5'-tetramethylbenzidine (TMB) and Ce3+ inducing aggregation induced emission (AIE) of Au nanoclusters (AuNCs). Under alkaline phosphatase (ALP), the ascorbic acid 2-phosphate (AA2P) can form ascorbic acid (AA) by dephosphorylation. The AA can reduce Ce4+ to generate Ce3+, which induced the AIE of AuNCs to enhance the fluorescence intensity of AuNCs. Meanwhile, unreacted Ce4+ oxidized TMB to form blue oxTMB. Thus, a dual-readout immunoassay was developed based on AIE of AuNCs and TMB as substrate. The limits of detection (LODs) were as low as 0.62 ng/mL for fluorescent assay and 0.81 ng/mL for colorimetric assay. The recoveries of OTA from corn were 94.4%-107.7% for the fluorescent mode and 93.7%-106.9% for the colorimetric mode. The results verified that the cerium ions triggered dual-readout immunoassay was reliable to sensitive detect OTA in corn samples.

Ratiometric Fluorescence Detection of Colorectal Cancer-Associated Exosomal miR-92a-3p with DSN-Assisted Signal Amplification by a MWCNTs@Au NCs Nanoplatform.

The detection of miRNA shows great promise in disease diagnosis. In this work, a ratiometric fluorescent biosensor based on multi-walled carbon nanotubes@gold nanoclusters (MWCNTs@Au NCs) and duplex-specific nuclease (DSN)-assisted signal amplification was fabricated for miRNA detection. Colorectal cancer (CRC)-associated miR-92a-3p extracted from exosomes was selected as the target. MWCNTs@Au NCs performs the dual functions of fluorescence quencher and internal fluorescence reference. In the absence of miR-92a-3p, an Atto-425-modified single-stranded DNA probe is adsorbed on MWCNTs@Au NCs, resulting in the quenching of Atto-425. In the presence of miR-92a-3p, the duplex is formed by hybridization of the probe and miR-92a-3p and leaves the MWCNTs@Au NCs, resulting in the fluorescence recovery of Atto-425. DSN can cleave the probe and result in the release of miR-92a-3p. The released miR-92a-3p can hybridize with other probes to form a signal amplification cycle. The fluorescence of MWCNTs@Au NCs remains stable and constitutes a ratiometric fluorescence system with that of Atto-425. A detection concentration interval of 0.1-10 pM and a limit of detection of 31 fM was obtained under optimized measurement conditions. In addition, the accuracy of the biosensor was validated by detecting the concentration of miR-92a-3p extracted from clinical exosome samples.

Targeting co-delivery of doxorubicin and gefitinib by biotinylated Au NCs for overcoming multidrug resistance in imaging-guided anticancer therapy.

Drug resistance and potential cardiotoxicity severely limit the DOX-mediated chemotherapy in clinical. Multi-drug combination is conducive to the realization of multi-modal synergy at the molecular level, which is crucial in drug dose optimization and improvement of therapeutic effect. In this work, fluorescent biotinylated Au Nanoclusters as an active targeting carrier was developed to realize real-time biological imaging and dual-drug delivery simultaneously. DNA toxin doxorubicin (DOX) and tyrosinase inhibitor gefitinib (GEF) were selected as dual-drug models for the treatment of human non-small cell lung cancer. The in vitro and in vivo results showed that dual-drug combination suppressed cancer cell growth more efficiently than any single formula at the same concentrations. GEF can block signaling in target cancer cells with mutated and overactive EGFR, thereby inhibiting tumor growth and metastasis and promoting tumor cell apoptosis. Combined with DOX chemotherapy, it will effectively overcome the problem of DOX resistance. In addition, the dual-drug delivery system produced excellent synergistic therapeutic effects without extra adverse toxicities. It provides a reference for the design and clinical application of the dual-drug delivery system.