Selenium Supplementation Sensor Based on Direct Electrochemistry of Urinary Selenosugar and Total Selenium.

Emerging point-of-care testing methods are extremely beneficial for personalized assessments of trace element metabolism including selenium (Se). Given the lack of timely evaluation methods for well-received Se fortification, an electrochemical solution was developed based on the recently identified urinary selenosugar (Sel) as a marker. The Se content of crude urine was rapidly determined (∼5 min), and the square-wave voltammetric responses of a Se-selective probe (SeSE) composed of liquid metal amalgam demonstrated comparable performance (e.g., detection limit: 19 nM) to central lab benchtop equipment within the physiological range. Meanwhile, SeSE enabled total urinary Se detection via a mere one-step oxidation. Additionally, SeSE was utilized to jointly assess the apparent internalization and utilization rate of two typical nutrients, selenite and selenomethionine, in a rat nutrition model, demonstrating consistent results with those obtained by HPLC-MS and ICP-MS. Upon systematic standardization directed by Ramaley's theory, SeSE was integrated into a battery-operated portable kit (dubbed "SeEye") with a micro electrochemical drive and tablet PC console for one-stop service trials in a local commercial scenario. This study establishes (1) a nutritive value classifier in a low-cost consumer electronic format and (2) noninvasive diagnostic technology for Se supplementation.

Tyrosine kinase receptor B attenuates liver fibrosis by inhibiting TGF-ß/SMAD signaling.

BACKGROUND AND AIMS: Liver fibrosis is a leading indicator for increased mortality and long-term comorbidity in NASH. Activation of HSCs and excessive extracellular matrix production are the hallmarks of liver fibrogenesis. Tyrosine kinase receptor (TrkB) is a multifunctional receptor that participates in neurodegenerative disorders. However, paucity of literature is available about TrkB function in liver fibrosis. Herein, the regulatory network and therapeutic potential of TrkB were explored in the progression of hepatic fibrosis. METHODS AND RESULTS: The protein level of TrkB was decreased in mouse models of CDAHFD feeding or carbon tetrachloride-induced hepatic fibrosis. TrkB suppressed TGF-ß-stimulated proliferation and activation of HSCs in 3-dimensional liver spheroids and significantly repressed TGF-ß/SMAD signaling pathway either in HSCs or in hepatocytes. The cytokine, TGF-ß, boosted Nedd4 family interacting protein-1 (Ndfip1) expression, promoting the ubiquitination and degradation of TrkB through E3 ligase Nedd4-2. Moreover, carbon tetrachloride intoxication-induced hepatic fibrosis in mouse models was reduced by adeno-associated virus vector serotype 6 (AAV6)-mediated TrkB overexpression in HSCs. In addition, in murine models of CDAHFD feeding and Gubra-Amylin NASH (GAN), fibrogenesis was reduced by adeno-associated virus vector serotype 8 (AAV8)-mediated TrkB overexpression in hepatocytes. CONCLUSION: TGF-ß stimulated TrkB degradation through E3 ligase Nedd4-2 in HSCs. TrkB overexpression inhibited the activation of TGF-ß/SMAD signaling and alleviated the hepatic fibrosis both in vitro and in vivo . These findings demonstrate that TrkB could be a significant suppressor of hepatic fibrosis and confer a potential therapeutic target in hepatic fibrosis.

Targeted delivery of CEBPA-saRNA for the treatment of pancreatic ductal adenocarcinoma by transferrin receptor aptamer decorated tetrahedral framework nucleic acid.

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

Point-of-Care Diagnosis on Selenium Nutrition Based on Time-Resolved Fluorometric Glycoaffinity Chromatography.

Given the lack of timely evaluation of the well-received selenium fortification, a neat lateral-flow chromatographic solution was constructed here by using the recently identified urinary selenosugar (Sel) as a strongly indicative marker. As there are no ready-made receptors for this synthetic standard, phenylboronic acid (PBA) esterification and Dolichos biflorus agglutinin (DBA) affinity joined up to pinch and pin down the analyte into a sandwich-type glycol complex. Pilot lectin screening on homemade glycan microarrays verified such a new pairing between dual recognizers as PBA-Sel-DBA with a firm monosaccharide-binding constant. To quell the sample autofluorescence, europium nanoparticles with efficient long-life afterglow were employed as conjugating probes under 1 µs excitation. After systematic process optimizations, the prepared Sel-dipstick achieved swift and sensitive fluorometry over the physiological level of the target from 0.1 to 10 µM with a detection limit down to 0.06 µM. Further efforts were made to eliminate matrix effects from both temperature and pH via an approximate formula. Upon completion, the test strips managed to quantify the presence of Sel in not just imitated but real human urine, with comparable results to those in the references. As far as we know, this would be the first in-house prototype for user-friendly and facile diagnosis of Se nutrition with fair accuracy as well as selectivity. Future endeavors will be invested to model a more traceable Se-supplementary plan based on the rhythmic feedback of Sel excretion.

Amplification of an Electrochemiluminescence-Emissive Aptamer into DNA Nanotags for Sensitive Fecal Calprotectin Determination.

The precision additive manufacturing and tessellated multitasking out of the structural DNA nanotechnology enable a configurable expression of densified electrochemiluminescent (ECL) complexes, which would streamline the bioconjugation while multiplying signals. Herein, a completely DNA-scaffold ECL "polyploid" was replicated out via the living course of rolling circle amplification. The amplicon carried the aptameric sequences of ZnPPIX/TSPP porphyrin as photoreactive centers that rallied at periodical intervals of the persistent extension into a close-packed nanoflower, ZnPDFI/II. Both microscopies and electrophoresis proved the robust nesting of guests at their deployed gene loci, while multispectral comparisons among cofactor substituents pinpointed the pivotal roles of singlet seclusion and Zn2+-chelation for the sake of intensive ECL irradiation. The adversity-resilient hydrogel texture made lipoidal filmogens as porphyrinic ECL prerequisites to be of no need at all, thus not only simplifying assay flows but also inspiring an in situ labeling plan. Upon bioprocessing optimization, an enriched probe ZnPDFIII was further derived that interpolated the binding motif related to calprotectin as validated by molecular docking and affinity titration. With it being a strongly indicative marker of inflammatory bowel disease (IBD), a competitive ECL aptasensing strategy was contrived, managing a signal-on and sensitive detection in mild conditions with a subnanogram-per-milliliter limit of detection by 2 orders of magnitude lower than the standard method as well as a comparable accuracy in clinical stool sample testing. Distinct from those conventional chemophysical rebuilding routes, this de novo biosynthetic fusion demonstrated a promising alternative toward ECL-source bioengineering, which may intrigue vibrant explorations of other ECL-shedding fabrics and, accordingly, a new bioanalytic mode downstream.

Double-activation of mitochondrial permeability transition pore opening via calcium overload and reactive oxygen species for cancer therapy.

BACKGROUND: Calcium ions (Ca2+) participates in various intracellular signal cascades and especially plays a key role in pathways relevant to cancer cells. Mitochondrial metabolism stimulated by calcium overload can trigger the opening of the mitochondrial permeability transition pore (MPTP), which leads to cancer cell death. METHODS: Herein, a mitochondrial pathway for tumour growth inhibition was built via the double-activation of MPTP channel. Fe2+ doped covalent organic frameworks (COF) was synthesised and applied as template to grow CaCO3 shell. Then O2 was storaged into Fe2+ doped COF, forming O2-FeCOF@CaCO3 nanocomposite. After modification with folic acid (FA), O2-FeCOF@CaCO3@FA (OFCCF) can target breast cancer cells and realize PDT/Ca2+ overload synergistic treatment. RESULTS: COF can induce the production of 1O2 under 650 nm irradiation for photodynamic therapy (PDT). Low pH and hypoxia in tumour microenvironment (TME) can activate the nanocomposite to release oxygen and Ca2+. The released O2 can alleviate hypoxia in TME, thus enhancing the efficiency of COF-mediated PDT. Abundant Ca2+ were released and accumulated in cancer cells, resulting in Ca2+ overload. Notably, the reactive oxygen species (ROS) and Ca2+ overload ensure the sustained opening of MPTP, which leads to the change of mitochondria transmembrane potential, the release of cytochrome c (Cyt c) and the activation of caspases 3 for cancer cell apoptosis. CONCLUSION: This multifunctional nanosystem with TME responded abilities provided a novel strategy for innovative clinical cancer therapy.

Development of pattern recognition based on nanosheet-DNA probes and an extendable DNA library.

Pattern recognition, also called "array sensing," is a recognition strategy with a wide and expandable analysis range, based on high-throughput analysis data. In this work, we constructed a sensor array for the identification of targets including bacterial pathogens and proteins by using FAM-labeled DNA probes and 2D nanosheet materials. We designed an ordered and extendible DNA library for the collection of recognition probes. Unlike traditional DNA probes with random and massive sequences, our DNA library was constructed following a 5-digit binary number (00000-11111, 0 = CCC, and 1 = TTT), and especially, 8 special symmetry sequences were chosen from the library. Two different nanosheet materials were used as the quencher. When targets were added, the interaction between DNA and the nanosheets was competitively affected, and as a result, the fluorescence signal changed accordingly. Finally, by using our fluorescent sensor array, 17 bacteria and 8 proteins were precisely recognized. We believe that our work has provided a simple and valuable strategy for the improvement of the recognition range and discrimination precision for the development of pattern recognition.

Fluorometric determination of HIV DNA using molybdenum disulfide nanosheets and exonuclease III-assisted amplification.

A convenient and ultrasensitive fluorometric method is described for the determination of HIV DNA. It exploits the strong difference in the affinities of MoS2 nanosheets for long ssDNA versus short oligonucleotide fragments. In addition, efficient signal amplification is accomplished by exonuclease III-assisted target recycling. When absorbed on the MoS2 nanosheets, the fluorescence of the FAM-labeled ssDNA probe (FP) is quenched. However, in the presence of HIV DNA, the FP hybridizes with target to form a duplex. As a result, the FP in the duplex will be stepwise hydrolyzed into short fragments by Exo III, and the fluorescence signal thus is retained because short fragments have low affinity for the MoS2 nanosheets. By using the Exo III-assisted target recycling amplification, the detection sensitivity is strongly improved. The sensor can detect DNA in a concentration as low as 5.3 pM (at an S/N ratio of 3), and the analytical range extends from 0.01 nM to 10 nM. The assay is simple, sensitive and specific, and conceivably represents a valuable tool in clinical studies related to the HIV. Graphical abstract Schematic presentation of fluorometric determination of HIV DNA based on molybdenum disulfide nanosheets and Exo III. When the fluorescence-tagged ssDNA probe hybridized with target to form a duplex, the Exo III-assisted target recycling amplification is generated. The method can detect as low as 5.3 pM HIV DNA.

DNA-templated silver nanoclusters for multiplexed fluorescent DNA detection.

Novel label-free/conjugation-free molecular beacons are designed based on DNA templated-silver nanoclusters for multiplexed DNA detection. The assay is implemented in solution, which makes it easy for the in-situ and real-time analysis. This study demonstrates a new method for multiplexd detection of biological molecules by using fluorescent Ag nanocluster-based molecular beacon probes.

Iodine Status of Infants and Toddlers under 2 Years of Age and Its Association with Feeding Behaviors and Maternal Iodine Status in Shanghai: A Quantile Regression Analysis.

It is crucial to provide adequate iodine nutrition to infants and toddlers for proper thyroid function and subsequent brain development. Infants are particularly vulnerable to iodine deficiency during the transition from a milk-based diet (breast milk and/or infant formula) to solid food. This study examines the current iodine levels of children during their first two years of life and investigates the association between these levels and feeding behaviors and the iodine status of their mothers in Shanghai, a city located in eastern China. A hospital-based cohort study was conducted to enroll mother-child pairs, where the child is aged 6-23 months, who visited community health service centers in the 16 districts of Shanghai, China. Data on socio-demographic factors and feeding behavior data were collected from the participants. The urinary iodine concentration (UIC) in both the young children and their mothers were analyzed. A total of 2282 mother-child pairs were included in this analysis. The median (p25-p75) UIC for lactating women, weaning women, and children were 121.3 µg/L (68.1-206.4 µg/L), 123.4 µg/L (58.4-227.2 µg/L), and 152.1 µg/L (75.8-268.3 µg/L), respectively. The UIC in children was found to be higher than that in their mothers (p < 0.001). Children who consumed less than 500 mL per day of formula milk in the last week had lower UICs compared with those who consumed 500 mL per day or more (p = 0.026). Furthermore, the children's UIC was positively correlated with the maternal UIC (rs = 0.285, p < 0.001). Multiple quantile regression analysis revealed a statistically significant positive association between maternal UIC and children's UIC between the 0.1 and 0.9 quantiles (all p < 0.001). We found that the iodine status of infants and toddlers, as well as of mothers, was sufficient. However, a large minority of children and mothers may be at risk of iodine deficiency. Furthermore, no associations between children's UIC and feeding behaviors were observed. Moreover, there was a positive correlation between the UIC of young children and their mothers.

Leveraging Concentration Imbalance-Driven DNA Circuit as an Operational Amplifier to Enhance the Sensitivity of Hepatitis B Virus DNA Detection with Hybridization-Responsive DNA-Templated Silver Nanoclusters.

Hepatitis B virus (HBV) infection remains a major global health concern, necessitating the development of sensitive and reliable diagnostic methods. In this study, we propose a novel approach to enhance the sensitivity of HBV DNA detection by leveraging a concentration imbalance-driven DNA circuit (CIDDC) as an operational amplifier, coupled with a hybridization-responsive DNA-templated silver nanocluster (DNA-AgNCs) nanoprobe named Q·C6-AgNCs. The CIDDC system effectively converts and amplifies the input HBV DNA into an enriched generic single-stranded DNA output, which subsequently triggers the fluorescence of the DNA-AgNCs reporter upon hybridization, generating a measurable signal for detection. By incorporating the DNA circuit, we not only achieved enhanced sensitivity with a lower detection limit of 0.11 nM but also demonstrated high specificity with single-base mismatch discriminability for HBV DNA detection. Additionally, this mix-and-detect assay format is simple, user-friendly, and isothermal. This innovative strategy holds promise for advancing molecular diagnostics and facilitating the effective management of HBV-related diseases.

A bioenergetically-active ploy (glycerol sebacate)-based multiblock hydrogel improved diabetic wound healing through revitalizing mitochondrial metabolism.

Diabetic wounds impose significant burdens on patients' quality of life and healthcare resources due to impaired healing potential. Factors like hyperglycemia, oxidative stress, impaired angiogenesis and excessive inflammation contribute to the delayed healing trajectory. Mounting evidence indicates a close association between impaired mitochondrial function and diabetic complications, including chronic wounds. Mitochondria are critical for providing energy essential to wound healing processes. However, mitochondrial dysfunction exacerbates other pathological factors, creating detrimental cycles that hinder healing. This study conducted correlation analysis using clinical specimens, revealing a positive correlation between mitochondrial dysfunction and oxidative stress, inflammatory response and impaired angiogenesis in diabetic wounds. Restoring mitochondrial function becomes imperative for developing targeted therapies. Herein, we synthesized a biodegradable poly (glycerol sebacate)-based multiblock hydrogel, named poly (glycerol sebacate)-co-poly (ethylene glycol)-co-poly (propylene glycol) (PEPGS), which can be degraded in vivo to release glycerol, a crucial component in cellular metabolism, including mitochondrial respiration. We demonstrate the potential of PEPGS-based hydrogels to improve outcomes in diabetic wound healing by revitalizing mitochondrial metabolism. Furthermore, we investigate the underlying mechanism through proteomics analysis, unravelling the regulation of ATP and nicotinamide adenine dinucleotide metabolic processes, biosynthetic process and generation during mitochondrial metabolism. These findings highlight the therapeutic potential of PEPGS-based hydrogels as advanced wound dressings for diabetic wound healing.

Designer cellular spheroids with DNA origami for drug screening.

Current in vitro models struggle to balance the complexity of human diseases with suitability for large-scale drug tests. While 3D cultures simulate human tissues, they lack cellular intricacy, and integrating these models with high-throughput drug screening remains a challenge. Here, we introduce a method that uses self-assembling nucleic acid nanostructures decorated living cells, termed NACs, to create spheroids with a customizable 3D layout. To demonstrate its uniqueness, our method effectively creates designer 3D spheroids by combining parenchymal cells, stromal cells, and immune cells, leading to heightened physiological relevance and detailed modeling of complex chronic diseases and immune-stromal interactions. Our approach achieves a high level of biological fidelity while being standardized and straightforward to construct with the potential for large-scale drug discovery applications. By merging the precision of DNA nanotechnology with advanced cell culture techniques, we are streamlining human-centric models, striking a balance between complexity and standardization, to boost drug screening efficiency.

Single-layer MoS2-based nanoprobes for homogeneous detection of biomolecules.

A single-layer MoS2 nanosheet exhibits high fluorescence quenching ability and different affinity toward ssDNA versus dsDNA. As a proof of concept, the MoS2 nanosheet has been successfully used as a sensing platform for the detection of DNA and small molecules.

Label-Free Detection of T4 Polynucleotide Kinase Activity and Inhibition via Malachite Green Aptamer Generated from Ligation-Triggered Transcription.

Polynucleotide kinase (PNK) is a key enzyme that is necessary for ligation-based DNA repair. The activity assay and inhibitor screening for PNK may contribute to the prediction and improvement of tumor treatment sensitivity, respectively. Herein, we developed a simple, low-background, and label-free method for both T4 PNK activity detection and inhibitor screening by combining a designed ligation-triggered T7 transcriptional amplification system and a crafty light-up malachite green aptamer. Moreover, this method successfully detected PNK activity in the complex biological matrix with satisfactory outcomes, indicating its great potential in clinical practice.

Topically applied fullerenols protect against radiation dermatitis by scavenging reactive oxygen species.

Adverse skin reactions caused by ionizing radiation are collectively called radiation dermatitis (RD), and the use of nanomedicine is an attractive approach to this condition. Therefore, we designed and large-scale synthesized fullerenols that showed free radical scavenging ability in vitro. Next, we pretreated X-ray-exposed cells with fullerenols. The results showed that pretreatment with fullerenols significantly scavenged intracellular reactive oxygen species (ROS) produced and enhanced the antioxidant capacity, protecting skin cells from X-ray-induced DNA damage and apoptosis. Moreover, we induced RD in mice by applying 30 Gy of X-ray irradiation, followed by treatment with fullerenols. We found that after treatment, the RD scores dropped, and the histological results systematically demonstrated that topically applied fullerenols could reduce radiation-induced skin epidermal thickening, collagen deposition and skin appendage damage and promote hair regeneration after 35 days. Compared with Trolamine cream, a typical RD drug, fullerenols showed superior radiation protection. Overall, the in vitro and in vivo experiments proved that fullerenols agents against RD.

Computational mining of endohedral C70 electrides: tri-metal alkali and alkaline-earth encapsulation.

C70 is the second most abundant fullerene next to C60. In this work, the exploration of C70 based electrides is proposed by theoretical encapsulation of group I/II trimetallic clusters into the C70 cage. Herein, we provide computational evidence that endohedral metallofullerenes M3@C70 (M = Li, Na, K, Be, Mg, Ca, Sr, Ba) can exist stably by calculating encapsulation energies and analyzing atom centered density matrix propagation molecular dynamics simulations. According to the results of the atoms in molecules analysis, electron localization functions and nonlinear optical properties, M3@C70 (M = Li, Be, Mg, Ca) fullerenes are identified as electrides. Interestingly, Li3@C70 and Be3@C70 are the systems with better electride performances among alkali metal and alkaline earth metal systems, respectively. It is worth noting that C70 can improve the polarizability and first hyperpolarizability of electrides compared with C60. Our work unearths the potential of M3@C70 electride systems and paves the way for the research of C70-based electrides.

Dietary zero-dimensional fullerene supplementation improves the meat quality, lipid metabolism, muscle fiber characteristics, and antioxidative status in finishing pigs.

With the increasing demand for high-quality pork, more nutritional substances have been studied for the regulation of meat quality. Zero-dimensional fullerenes (C60) can modulate the biological behavior of a variety of cell lines and animals. In this study, we report the biological effects of C60 on finishing pigs at different concentrations. A total of 24 barrows (Duroc × Large White × Landrace), with an average body weight of 21.01 ± 0.98 kg, were divided into 3 groups and each treated daily with C60 (100 or 200 mg per kg feed) or a control diet until the end of the experiment. Our results showed that dietary C60 supplementation improved flesh color, marbling scores, and flavor amino acid contents of longissimus dorsi (LD) of growing-finishing pigs (P < 0.05). C60 improved meat quality by regulating lipid metabolism and muscle fiber morphology by mediating the expression of genes, L-lactic dehydrogenase (LDH), myosin heavy chain (MyHC) IIa, MyHCIIb, peroxisome proliferator-activated receptor γ (PPARγ), and fatty acid transport protein 1 (FATP1) (P < 0.05). Moreover, C60 substantially promoted the mRNA expression of antioxidant enzyme genes (P < 0.05), which also contributed to improving meat quality. These findings have important implications for the application of C60 in the livestock industry, especially for improving the meat quality of fattening pigs.

Ambient-pressure synthesis of ethylene glycol catalyzed by C60-buffered Cu/SiO2.

Bulk chemicals such as ethylene glycol (EG) can be industrially synthesized from either ethylene or syngas, but the latter undergoes a bottleneck reaction and requires high hydrogen pressures. We show that fullerene (exemplified by C60) can act as an electron buffer for a copper-silica catalyst (Cu/SiO2). Hydrogenation of dimethyl oxalate over a C60-Cu/SiO2 catalyst at ambient pressure and temperatures of 180° to 190°C had an EG yield of up to 98 ± 1%. In a kilogram-scale reaction, no deactivation of the catalyst was seen after 1000 hours. This mild route for the final step toward EG can be combined with the already-industrialized ambient reaction from syngas to the intermediate of dimethyl oxalate.

Iridium Complex-Loaded Sorafenib Nanocomposites for Synergistic Chemo-photodynamic Therapy of Hepatocellular Carcinoma.

Although sorafenib, a multi-kinase inhibitor, has provided noteworthy benefits in patients with hepatocellular carcinoma (HCC), the inevitable side effects, narrow therapeutic window, and low bioavailability seriously affect its clinical application. To be clinically distinctive, innovative drugs must meet the needs of reaching tumor tissues and cause limited side effects to normal organs and tissues. Recently, photodynamic therapy, utilizing a combination of a photosensitizer and light irradiation, was selectively accumulated at the tumor site and taken up effectively via inducing apoptosis or necrosis of cancer cells. In this study, a nano-chemo-phototherapy drug was fabricated to compose an iridium-based photosensitizer combined with sorafenib (IPS) via a self-assembly process. Compared to the free iridium photosensitizer or sorafenib, the IPS exhibited significantly improved therapeutic efficacy against tumor cells because of the increased cellular uptake and the subsequent simultaneous release of sorafenib and generation of reactive oxygen species production upon 532 nm laser irradiation. To evaluate the effect of synergistic treatment, cytotoxicity detection, live/dead staining, cell proliferative and apoptotic assay, and Western blot were performed. The IPS exhibited sufficient biocompatibility by hemolysis and serum biochemical tests. Also, the results suggested that IPS significantly inhibited HCC cell proliferation and promoted cell apoptosis. More importantly, marked anti-tumor growth effects via inhibiting cell proliferation and promoting tumor cell death were observed in an orthotopic xenograft HCC model. Therefore, our newly proposed nanotheranostic agent for combined chemotherapeutic and photodynamic therapy notably improves the therapeutic effect of sorafenib and has the potential to be a new alternative option for HCC treatment.