IR780-based diffuse fluorescence tomography for cancer detection.

IR780 iodide is a commercially available targeted near-infrared contrast agent for in vivo imaging and cancer photodynamic or photothermal therapy, whereas the accumulation, dynamics, and retention of IR780 in biological tissue, especially in tumor is still under-explored. Diffuse fluorescence tomography (DFT) can be used for localization and quantification of the three-dimensional distribution of NIR fluorophores. Herein, a homemade DFT imaging system combined with tumor-targeted IR780 was utilized for cancer imaging and pharmacokinetic evaluation. The aim of this study is to comprehensively assess the biochemical and pharmacokinetic characteristics of IR780 with the aid of DFT imaging. The optimal IR780 concentration (20 µg/mL) was achieved first. Subsequently, the good biocompatibility and cellar uptake of IR780 was demonstrated through the mouse acute toxic test and cell assay. In vivo, DFT imaging effectively identified various subcutaneous tumors and revealed the long-term retention of IR780 in tumors and rapid metabolism in the liver. Ex vivo imaging indicated IR780 was mainly concentrated in tumor and lung with significantly different from the distribution in other organs. DFT imaging allowed sensitive tumor detection and pharmacokinetic rates analysis. Simultaneously, the kinetics of IR780 in tumors and liver provided more valuable information for application and development of IR780.

Comparative Assessment of In Vitro Xanthine Oxidase and α-Glucosidase Inhibitory Activities of Cultured Cambial Meristematic Cells, Adventitious Roots, and Field-Cultivated Ginseng.

Panax ginseng, a traditional Chinese medicine with a history spanning thousands of years, faces overexploitation and challenges related to extended growth periods. Tissue-cultured adventitious roots and stem cells are alternatives to wild and field-cultivated ginseng. In this study, we assessed the in vitro xanthine oxidase and α-glucosidase inhibitory activities of saponin extracts among cultured cambial meristematic cells (CMC), adventitious ginseng roots (AGR), and field-cultivated ginseng roots (CGR). The xanthine oxidase (XO) and α-glucosidase inhibitory activities were determined by uric acid estimation and the p-NPG method, respectively. Spectrophotometry and the Folin-Ciocalteu, aluminum nitrate, and Bradford methods were employed to ascertain the total saponins and phenolic, flavonoid, and protein contents. The calculated IC50 values for total saponin extracts against XO and α-glucosidase were 0.665, 0.844, and >1.6 mg/mL and 0.332, 0.745, and 0.042 mg/mL for AGR, CMC, CGR, respectively. Comparing the total saponin, crude protein, and total phenolic contents revealed that AGR > CMC > CGR. To the best of our knowledge, this study presents the first report on the in vitro comparison of xanthine oxidase and α-glucosidase inhibitory activities among AGR, CMC, and CGR. The findings offer valuable insights into the development of hypoglycemic and antihyperuricemic medicinal, nutraceutical, and functional products utilizing AGR and CMC.

Biotransformation of American Ginseng Stems and Leaves by an Endophytic Fungus Umbelopsis sp. and Its Effect on Alzheimer's Disease Control.

BACKGROUND: Common ginsenosides can be transformed into rare ginsenosides through microbial fermentation, and some rare ginsenosides can prevent Alzheimer's disease (AD). This study aimed to transform common ginsenosides into rare ginsenosides through solid-state fermentation of American ginseng stems and leaves (AGSL) by an endophytic fungus and to explore whether fermented saponin extracts prevent AD. METHODS: The powders of AGSL were fermented in a solid state by endophytic fungus. Total saponins were extracted from fermentation products using the methanol extraction method. The types of saponins were analyzed by liquid chromatography mass spectrometry (LC/MS). The Aß42 concentration and ß-secretase activity were measured by ELISA for the prevention of AD. RESULTS: After AGSL was fermented by an endophytic fungus NSJG, the total saponin concentration of the fermented extract G-SL was higher than the unfermented CK-SL. Rare ginsenoside Rh1 was newly produced and the yield of compound K (561.79%), Rh2 (77.48%), and F2 (40.89%) was increased in G-SL. G-SL had a higher inhibition rate on Aß42 concentration (42.75%) and ß-secretase activity (42.22%) than CK-SL, possibly because the rare ginsenoside Rh1, Rh2, F2, and compound K included in it have a strong inhibitory effect on AD. CONCLUSION: The fermented saponin extracts of AGSL show more inhibition effects on AD and may be promising therapeutic drugs or nutrients for AD.

Dynamic ultrasound molecular-targeted imaging of senescence in evaluation of lapatinib resistance in HER2-positive breast cancer.

BACKGROUND: Prolonged treatment of HER2+ breast cancer with lapatinib (LAP) causes cellular senescence and acquired drug resistance, which often associating with poor prognosis for patients. We aim to explore the correlation between cellular senescence and LAP resistance in HER2+ breast cancer, screen for molecular marker of reversible senescence, and construct targeted nanobubbles for ultrasound molecular imaging to dynamically evaluate LAP resistance. METHODS AND RESULTS: In this study, we established a new cellular model of reversible cellular senescence using LAP and HER2+ breast cancer cells and found that reversible senescence contributed to LAP resistance in HER2+ breast cancer. Then, we identified ecto-5'-nucleotidase (NT5E) as a marker of reversible senescence in HER2+ breast cancer. Based on this, we constructed NT5E-targeted nanobubbles (NT5E-FITC-NBs) as a new molecular imaging modality which could both target reversible senescent cells and be used for ultrasound imaging. NT5E-FITC-NBs showed excellent physical and imaging characteristics. As an ultrasound contrast agent, NT5E-FITC-NBs could accurately identify reversible senescent cells both in vitro and in vivo. CONCLUSIONS: Our data demonstrate that cellular senescence-based ultrasound-targeted imaging can identify reversible senescence and evaluate LAP resistance effectively in HER2+ breast cancer cells, which has the potential to improve cancer treatment outcomes by altering therapeutic strategies ahead of aggressive recurrences.

Optimization of Fermentation Conditions and Product Identification of a Saponin-Producing Endophytic Fungus.

BACKGROUND: Some fungal endophytes isolated from P. ginseng may present a new method of obtaining saponins. This experiment aimed to optimize the total saponin yield produced through in vitro fermentation by an endophytic fungus and analyze its saponin species in the fermented extract. METHODS: Fermentation protocols were optimized with a uniform design and verified through regression analysis to maximize the total saponin yield. The saponin types under optimal fermentation conditions were then identified and analyzed using Liquid Chromatography-Mass Spectrometry. RESULTS: The Trametes versicolor strain NSJ105 (gene accession number: OR144428) isolated from wild ginseng could produce total saponins. The total saponin yield could be increased more than two-fold through the optimization of fermentation conditions. The concentration of the total saponins achieved by the verified protocol 105-DP was close to the predicted value. The fermentation conditions of the 105-DP protocol were as follows: potato concentration 97.3 mg/mL, glucose concentration 20.6 mg/mL, inoculum volume 2.1%, fermentation broth pH 2.1, fermentation temperature 29.2 °C, and fermentation time 6 d. It was detected and analyzed that the fermented extract of 105-DP contained the ginsenosides Rf and Rb3. CONCLUSION: The endophytic fungus Trametes versicolor strain NSJ105 has potential application value in saponin production.

Apoptin and apoptotic protease-activating factor 1 plasmid-assisted multi-functional nanoparticles in hepatocellular carcinoma therapy.

Cancer drugs usually have side effects in chemotherapy. Apoptin, a protein recognized by its good therapeutical effect on tumors and innocuous to body, is employed to treat hepatocellular carcinoma (HCC). As our previous data shown, the efficiency of apoptin protein might be limited by the protein of apaf-1. Therefore, we designed the multi-functional nanoparticles (MFNPs) encapsulating apoptin and apaf-1 plasmids by layer-by layer assembly. The NPs could release drugs into tumor site specifically and had good compatibility to normal cells and tissues. The groups of biotin, ε-polylysine, and nuclear localization signal in MFNPs conferred NPs the capabilities to enter cancer cells specifically, escape lysosome and enter the nucleus, respectively. In vitro inhibition experiment and in vivo anti-tumor therapy confirmed MFNPs as an excellent carrier to treat HCC. In addition, the dual-drug system was superior to any of the single-drug system. The mechanism analysis proved that supplement of the protein of apaf-1 might enhance apoptosome formation, causing the increase of therapeutical efficacy.

High-resolution 3D nanoprinting based on two-step absorption via an integrated fiber-coupled laser diode.

Three-dimensional (3D) laser nanoprinting with high resolution and low cost is highly desirable for fabricating arbitrary 3D structures with fine feature size. In this work, we use a 405-nm integrated fiber-coupled continuous wave (cw) laser diode to establish an easy-to-build 3D nanoprinting system based on two-step absorption. Two-dimensional (2D) gratings with a sub-150-nm period and 3D woodpile nanostructures with a lateral period of 350 nm have been printed at a low speed. At a faster scan velocity of 1000 µm/s, 2D gratings with sub-200-nm resolution and sub-50-nm linewidth can still be fabricated with laser power less than 1 mW. The two-step absorption of the used benzil initiator enables us to use a second cw laser with 532-nm wavelength to enhance the polymerization with sub-100-nm feature size when starting with insufficient 405-nm laser power, which possess the potential to find applications in high-speed high-resolution parallel-writing and in situ manipulation.

Self-assembly of amphiphilic polyelectrolytes in trivalent salt solution.

Multivalent salt plays important roles in polyelectrolyte (PE) systems. Some special effects, such as ion mediated electrostatic correlation and reentrant condensation can be induced in the presence of multivalent salt. In this work, the self-assembly behaviors of diblock PEs in trivalent salt solutions are mainly investigated by molecular dynamics (MD) simulations, and partial results are qualitatively verified by experiments. The electrostatic correlation between PE chains and trivalent counterions is first enhanced with the increase of salt concentration, and then the large complexes of co-ions and trivalent counterions reduce the correlation at the excessive salt regime. Therefore, the electrostatic correlation mediated by trivalent ions shows a non-monotonic dependence on salt content. It should be noted that one-dimensional chain-like and two-dimensional planar network supra-micellar structures are obtained at different concentrations of PEs. It is the strong electrostatic correlation mediated by trivalent counterions that leads to the cross-linking of micelles, and homogeneous spherical micelles rather than anisotropic micelles are used as building blocks. Both of these supra-micellar structures predicted by simulations are qualitatively confirmed by experiments, and a micron sized long polymer chain and planar networks of inter-connected micelles are demonstrated in transmission electron microscopy (TEM) images. Reentrant behavior of the assembled micelles is demonstrated at a lower polymer concentration. The transitions from a dispersed micellar phase to a fully phase separated phase (where all the copolymer chains aggregate into one micelle to precipitate out of the solution) and to the re-dissolution of micelles are displayed with an increase in trivalent salt. The non-monotonic dependence of electrostatic correlation on the salt content is well displayed by the four states of the assembled micelles: (i) dispersed micelles, (ii) a single micelle comprising of all copolymer chains, (iii) micellar complex, and (iv) re-dispersed micelles. Our analysis may provide guidance for cross-linking of isotropic micelles into superstructures.

High-Performance Perovskite Light-Emitting Diodes Enabled by Passivating Defect and Constructing Dual Energy-Transfer Pathway through Functional Perovskite Nanocrystals.

Quasi-2D perovskites have emerged as a promising luminescent material for perovskite light-emitting diodes (Pe-LEDs). However, efficiency and stability are still obstacles to practical application due to numerous defects and inefficient energy transfer of perovskite films. Herein, functional phenethylammonium bromine-modified CsPbBr3 nanocrystals (PEA-CsPbBr3 NCs) are first introduced as multifunctional additive to simultaneously improve abovementioned problems. PEA-CsPbBr3 NCs not only serve as heteronuclear seeds and trigger growth, thus greatly reducing leakage current, but also deliver Cs+ and Br- to passivate the intrinsic defects inside film. More importantly, the PEA-CsPbBr3 construct a new carrier-transfer pathway from the small-n phase of the quasi-2D perovskite to the PEA-CsPbBr3 , which not only accelerates the energy-transfer process but also promotes radiation recombination of carriers due to stronger quantum confinement effect. Afterward, the poly(3,4-ethylenedioxythiophene):polystyrene sulfonate/poly[9,9-dioctylfluoreneco-N-[4-(3-methylpropyl)]diphenylamine]:black phosphorus quantum dot double hole-transport layer is successfully constructed to enhance its carrier-injection and charge-transport abilities. Consequently, a champion external quantum efficiency of 25.32% and maximal brightness of 128 842 cd m-2 are achieved, which is the record efficiency of the quasi-2D Pe-LED with pure green emission at 530 nm. Moreover, an impressive 174 min lifetime is obtained at T50 , which is about five times longer than the control device.

Impact of Asymptomatic Neurosyphilis on Patients Quality of Life and Social Stigma.

Background/Objectives: Neurosyphilis is a disease caused by Treponema pallidum when it invades the central nervous system. Asymptomatic neurosyphilis (ANS) is one of the most common types of neurosyphilis, however it is often misdiagnosed. This study aimed to explore the impact of ANS on patient's quality of life and social stigma. Methods: A total of 159 ANS patients were diagnosed by their serology and cerebrospinal fluid. These patients' stigma and quality of life were assessed separately through the Social Impact Scale (SIS) and the Easy Response Questionnaire. Results: The average age was 36.25±8.36 years old, and 114 patients were males (71.69%). The serum syphilis test of 159 selected patients was positive, and the indicators of nucleus cells, protein quantification, and syphilis antibodies in the cerebrospinal fluid met the criteria for ANS. The total stigma score was (40.23 ±10.12), with the scores of the different entries being clearly differentiated, with the highest being the 15th entry (I feel I need to keep my illness a secret), with an average score of 3.15/4. Conclusion: Patients with asymptomatic neurosyphilis may feel social stigma and are more negative when facing their disease. Health-care workers should be aware of the particular aspects of their condition and pay special attention to the need for patient privacy.

Biochemical and Metabolomic Responses of Antarctic Bacterium Planococcus sp. O5 Induced by Copper Ion.

Heavy metal pollution in the Antarctic has gone beyond our imagination. Copper toxicity is a selective pressure on Planococcus sp. O5. We observed relatively broad tolerance in the polar bacterium. The heavy metal resistance pattern is Pb2+ > Cu2+ > Cd2+ > Hg2+ > Zn2+. In the study, we combined biochemical and metabolomics approaches to investigate the Cu2+ adaptation mechanisms of the Antarctic bacterium. Biochemical analysis revealed that copper treatment elevated the activity of antioxidants and enzymes, maintaining the bacterial redox state balance and normal cell division and growth. Metabolomics analysis demonstrated that fatty acids, amino acids, and carbohydrates played dominant roles in copper stress adaptation. The findings suggested that the adaptive mechanisms of strain O5 to copper stress included protein synthesis and repair, accumulation of organic permeable substances, up-regulation of energy metabolism, and the formation of fatty acids.

Exploration of plant-derived natural polyphenols toward COVID-19 main protease inhibitors: DFT, molecular docking approach, and molecular dynamics simulations.

Recent outbreaks of coronavirus have brought serious challenges to public health around the world, and it is essential to find effective treatments. In this study, the 3C-like proteinase (3CLpro) of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been considered as an important drug target because of its role in viral replication. We initially optimized 251 compounds at the PM7 level of theory for docking with 3CLpro, and then we selected the top 12 compounds for further optimization with the B3LYP-D3/6-311G** method and obtained the top four compounds by further molecular docking. Quantum chemistry calculations were performed to predict molecular properties, such as the electrostatic potential and some CDFT descriptors. We also performed molecular dynamics simulations and free energy calculations to determine the relative stability of the selected four potential compounds. We have identified key residues controlling the 3CLpro/ligand binding from per-residue based decomposition of the binding free energy. Convincingly, the comprehensive results support the conclusion that the compounds have the potential to become a candidate for anti-coronavirus treatment.

Targeting delivery of synergistic dual drugs with elastic PEG-modified multi-functional nanoparticles for hepatocellular carcinoma therapy.

Integration of multiple advantages in one system has been leveraged to overcome multiple biological barriers in anti-tumor therapeutic strategies. In this study, multi-functional nanoparticles (MFNPs) are constructed by layer-by-layer method. MFNPs are modified with pH-responsive elastic PEG-GPC3MAb (glypican-3 monoclonal antibody), which draws back into PEG layer in blood and normal tissues; and stretches out of MFNPs surface in the acidic tumor microenvironment. It is proved that blank MFNPs have good biocompatibility by MTT and acute toxicity assays. Elastic PEG chains are able to respond sensitively in different pH environments (6.8 and 7.4), which is demonstrated by transmission electron microscope (TEM) and 1H nuclear magnetic resonance (1H NMR). In vitro experiments show that MFNPs have better specificity to Hepa 1-6 cells, can escape from lysosomes, and are able to increase the nuclear delivery of dual drugs for synergistic therapy, which are proved by flow cytometry, MTT, confocal laser scanning microscopy, and western blot studies. In vivo experiments indicate that MFNPs show extending circulation half-life in blood, promoting localization into tumor tissues, improving the therapeutic efficacy of BAL b/c nude mice with subcutaneous tumors. Overall, the results indicate that FMNPs are a potential candidate for hepatocellular carcinoma therapy.

Mesonia hitae sp. nov., isolated from the seawater of the South Atlantic Ocean.

A Gram-negative, non-motile, non-spore-forming, aerobic and short rod-shaped bacterial strain R32T, was isolated from seawater of the South Atlantic Ocean. Strain R32T grew at 10-40 °C (optimum 28 °C), at pH 6.0-8.0 (optimum 7.0), and in the presence of 3-8 % NaCl (w/v) (optimum 5 %). Cells were oxidase- and catalase-positive. The 16S rRNA gene sequence of strain R32T shared the highest similarities with Mesonia oceanica (98.3 %), followed by Salegentibacter salarius (93.0 %), Salegentibacter mishustinae (92.8 %), Salegentibacter salegens (92.5 %) and Mesonia maritima (92.4 %). The dominant fatty acids were iso-C15 : 0 (32.7 %) and iso-C17 : 0 3-OH (21.1 %). Menaquinone-6 (MK-6) was detected as the sole respiratory quinone. The polar lipids found were phosphatidylethanolamine, three aminolipids and three unidentified lipids. The DNA G+C content was 35.0 mol%. The ANI value and dDDH value between strain R32T and the Salegentibacter and Mesonia species were 70.5-85.8 % and 18.7-30.5 %, respectively. Based on the results of the polyphasic characterization, strain R32T is considered to represent a novel species of the genus Mesonia, for which the name Mesonia hitae sp. nov. is proposed. The type strain is R32T (=MCCC 1A09780T=KCTC 72004T).

Positive psychological intervention for anxiety, depression and coping in subjects addicted to online games.

BACKGROUND: Addiction to online games is not uncommon. The patients usually refuse to take medications and present with affective symptoms such as anxiety, depression and negative coping styles. Psychological intervention based on positive psychology is a promising treatment for such patients. AIM: To evaluate the effect of positive psychological intervention on anxiety, depression and coping in people addicted to online games. METHODS: This self-controlled study included 89 people addicted to online games, who received treatment at Hangzhou Seventh People's Hospital, Hangzhou, China in 2019. The Hamilton Anxiety Scale, Hamilton Depression Scale and Trait Coping Style Questionnaire were administered to evaluate the anxiety, depression and coping style among these people. Psychological intervention based on positive psychology was provided for 6 wk followed by another evaluation. The results were compared against those from the previous evaluation. RESULTS: After 6 wk of psychological intervention, 89 people achieved a significant improvement in the Hamilton Anxiety Scale and Hamilton Depression Scale-24 scales. The score for positive coping style in Trait Coping Style Questionnaire was significantly improved, while that of the negative coping style decreased significantly (P < 0.05). CONCLUSION: Psychological intervention based on positive psychology alleviated affective symptoms, such as anxiety and depression, in subjects addicted to online games. Psychological intervention corrected negative coping style, thereby improving mental health.

Study of the Photoluminescence Characteristics of 4,4'-((1E,1'E)-Quinoxaline-2,3-diylbis(ethene-2,1-diyl))bis(N,N-dimethylaniline).

A comparative investigation on the photophysical properties of a quinoxaline derivative 4,4'-((1E,1'E)-quinoxaline-2,3-diylbis(ethene-2,1-diyl))bis(N,N-dimethylaniline) (QDMA2) was performed by employing many spectroscopies. Based on the pump-dump/push-probe measurement, it is found that a solvent-stabilized charge-transfer state can participate in the relaxation of excited QDMA2 with increasing solvent polarity. Meanwhile, the aggregated QDMA2 molecules were engineered into the organic light-emitting diode test, which showed a correlated color temperature value of 1875 K. With the help of a diamond anvil cell, the pressure-dependent photoluminescence of aggregated QDMA2 shows that the intermolecular interaction can affect the color and intensity of photoluminescence through adjusting the band gap and irradiative channel of the aggregated molecules. These results are important for understanding the structure-property relationships and the rational design of functional materials for optoelectronic applications.

Diversity and Antiaflatoxigenic Activities of Culturable Filamentous Fungi from Deep-Sea Sediments of the South Atlantic Ocean.

Despite recent studies, relatively few are known about the diversity of fungal communities in the deep Atlantic Ocean. In this study, we investigated the diversity of fungal communities in 15 different deep-sea sediments from the South Atlantic Ocean with a culture-dependent approach followed by phylogenetic analysis of ITS sequences. A total of 29 fungal strains were isolated from the 15 deep-sea sediments. These strains belong to four fungal genera, including Aspergillus, Cladosporium, Penicillium, and Alternaria. Penicillium, accounting for 44.8% of the total fungal isolates, was a dominant genus. The antiaflatoxigenic activity of these deep-sea fungal isolates was studied. Surprisingly, most of the strains showed moderate to strong antiaflatoxigenic activity. Four isolates, belonging to species of Penicillium polonicum, Penicillium chrysogenum, Aspergillus versicolor, and Cladosporium cladosporioides, could completely inhibit not only the mycelial growth of Aspergillus parasiticus mutant strain NFRI-95, but also the aflatoxin production. To our knowledge, this is the first report to investigate the antiaflatoxigenic activity of culturable deep-sea fungi. Our results provide new insights into the community composition of fungi in the deep South Atlantic Ocean. The high proportion of strains that displayed antiaflatoxigenic activity demonstrates that deep-sea fungi from the Atlantic Ocean are valuable resources for mining bioactive compounds.

Scanning Ultrafast Spectral Dynamics of Triphenylamine-Modified Vinylbenzothiazole Derivative: Role of Solvent Polarity and Temperature.

The photophysical properties of a donor-acceptor compound based on triphenylamine-modified vinylbenzothiazole derivative (BTTM) are investigated by multispectral techniques. Based on the pump-probe and pump-dump/push-probe technique, it is found that the hybridized localized excited (LE) and charge transfer (CT) state (HLCT) participates in the relaxation process of excited BTTM. The excited state is the LE-dominated HLCT state in cyclohexane; then it evolves to the CT-dominated HLCT state in a high polarity solvent. Meanwhile, a new intermediate state named the HLCT' state also exists in a high polar solvent. When the temperature of BTTM film drops, the increasing photoluminescence (PL) lifetime and PL quantum yield are assigned to the nonradiative recombination inactivation. The pump-probe data show that exciton-exciton annihilation originating from exciton collision gradually increases owing to the weakening of phonon-exciton scattering at low temperature. Our results provide comprehensive insight into the optoelectronic properties of organic molecules.

Isolation of a novel deep-sea Bacillus circulus strain and uniform design for optimization of its anti-aflatoxigenic bioactive metabolites production.

The deep-sea bacterium strain FA13 was isolated from the sediment of the South Atlantic Ocean and identified as Bacillus circulans based on 16S ribosomal DNA sequence. Through liquid fermentation with five media, the cell-free supernatant fermented with ISP2 showed the highest inhibition activities against mycelial growth of Aspergillus parasiticus mutant strain NFRI-95 and accumulation of norsolorinic acid, a precursor for aflatoxin production. Based on ISP2, uniform design was used to optimize medium formula and fermentation conditions. After optimization, the inhibition efficacy of the 20-time diluted supernatant against A. parasiticus NFRI-95 mycelial growth and aflatoxin production was increased from 0-23.1% to 100%. Moreover, compared to the original protocol, medium cost and fermentation temperature were significantly reduced, and dependence on seawater was completely relieved, thus preventing the fermentor from corrosion. This is the first report of a deep-sea microorganism which can inhibit A. parasiticus NFRI-95 mycelial growth and aflatoxin production.

Dual-Targeting Nanoparticles: Codelivery of Curcumin and 5-Fluorouracil for Synergistic Treatment of Hepatocarcinoma.

Chemotherapy has been the standard for cancer therapy, but the nonspecific cytotoxicity of chemotherapeutic agents and drug resistance of tumor cells has limited its efficacy. However, multidrug combination therapy and targeting therapy have resulted in enhanced anticancer effects and have become increasingly important strategies in clinical applications. In this study, a biotin-/lactobionic acid-modified poly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol) (BLPP) copolymer was synthesized, and curcumin- and 5-fluorouracil-loaded nanoparticles (BLPPNPs/C + F) were prepared to enhance the treatment of hepatocellular carcinoma. Blank BLPPNPs were shown to have great biocompatibility via both in vitro and in vivo studies. Good targeting of tumor cells of BLPPNPs was confirmed by flow cytometry, fluorescence microscopy, and biodistribution. The synergistic anticancer effects of BLPPNPs/C + F were demonstrated by cytotoxicity and animal studies, while western blotting was used to further verify the synergistic effect of curcumin and 5-fluorouracil. The dual-targeting and drug-loaded codelivery nanosystem demonstrated higher cellular uptake and stronger cytotoxicity for tumor cells. Therefore, these dual-targeting NPs are a promising codelivery carrier that could be made available for cellular targeting of anticancer drugs to achieve better intracellular delivery and synergistic anticancer efficacy.