Glycol Derivatives Research Articles

Synthesis and intensive analysis of antibody labeled single core magnetic nanoparticles for targeted delivery to the cell membrane

This work is dedicated to the synthesis and characterization of antibody labeled magnetic nanoparticles as promising tool for biomedical applications. Single core magnetic nanoparticles were synthesized by thermal decomposition technique, followed by surface modification with ligand based on polyethylene glycol derivative. Fluorochrome-labeled species-specific antibodies were covalently conjugated to MNPs through a polyethylene glycol linker. The immunofluorescent analysis showed the successful binding of anti-α-tubulin or anti-β-catenin antibodies conjugated MNPs to α-tubulin and β-catenin in 4T1 cells of mouse breast cancer.

Derivatization increases mosquito larvicidal activity of the sesquiterpene lactone parthenin isolated from the invasive weed Parthenium hysterophorus.

Extracts of the invasive weed Parthenium hysterophorus (Asteraceae) have been shown to possess larvicidal activity against a wide range of disease vectors. However, the phytochemicals responsible for the larvicidal activity from this plant remain unidentified. Here, we isolated the major sesquiterpene lactone, parthenin (1) from the plant and synthesized two derivatives [ethylene glycol (2) and azide (3) derivatives] targeting the α,β-unsaturated carbonyl group, previously known to account for its biological activity such as toxicity towards cells and microorganism. All three compounds were screened for larvicidal activity against the African malaria vector Anopheles gambiae. The larval mortality of ethylene glycol derivative (2) and 2α-azidocoronopilin (3) were approximately two-four-fold higher than that of parthenin (1) and neem oil with LC50 values of 37 and 66 mg L-1 , respectively. Parthenin (1) and the positive control, neem oil, had comparable median lethal concentration (LC50 ) values of 154 and 121 mg L-1 , respectively. In assays with binary combinations of the three compounds, larvicidal activity followed the order: parthenin (1) + 2α-azidocoronopilin (3) (LC50 = 14 mg L-1 ) > parthenin (1) + ethylene glycol derivative (2) (LC50 = 109 mg L-1 ), > blend of 2α-azidocoronopilin (3) and ethylene glycol derivative (2) (LC50 = 200 mg L-1 ). Structural modification of parthenin (1) through addition of hydroxyl groups increases its larvicidal effects. These findings advance the use of structural modification approach in the development of lead chemical molecules for potential exploitation in larval source management.

Potential urinary monitoring of the enhanced permeability and retention effect using MMP-2-responsive poly(ethylene glycol) derivatives

The enhanced permeability and retention (EPR) effect is fundamental to tumor-targeted drug delivery using nanoparticles. However, recent studies reported heterogeneity of the EPR effect, and companion diagnostics are considered to be key to predicting and optimizing the benefits of the EPR effect. Here, as a new material to simply endow the function of companion diagnostics to nanoparticles, we designed a poly(ethylene glycol) (PEG) derivative conjugated with low molecular fluorescent dye through synthetic substrate linker that can be cleaved in response to MMP-2, which is overexpressed in tumor extracellular matrix. Upon tumor accumulation, the low molecular fluorescent dye is released from the PEG and quickly excreted to urine, thereby reporting its tumor accumulation level as a fluorescent signal in the urine. In this study, this urinary reporter was conjugated with albumin, and the functionalized albumin exhibited efficient accumulation in various tumors. Importantly, the functionalized albumin exhibited significantly higher excretion of the fluorescent dye in the urine in mice with tumors compared with those without tumors. The PEG derivatives proposed in this study may be a promising tool to predict the EPR effect in individual cancer patients.

Technological aspects of synthesis of poly(ethylene glycol) mono-1-propenyl ether monomers

Abstract For the first time, the technological aspects of the highly productive and selective synthesis of UV-reactive poly(ethylene glycol) mono-1-propenyl ether monomers was developed. The solvent-free isomerization of model commercial available 2-allyloxyethanol and allyloxypoly(ethylene glycol) derivatives, type Allyl–[OCH2CH2] n –OH, n = 1–5, into a 1-propenyl derivative under the homogeneous catalysis conditions using the ruthenium complexes were evaluated. The effect of a various reaction conditions (i.e. the concentration of [Ru] complex, the reaction temperature, reaction gas atmosphere) together with trace amounts of allyl hydroperoxides formed via autoxidation reaction of allyl substrates on the productivity of catalyst was examined in detail. Moreover, the significant role of the allyl substrate structures on the catalytic activity of ruthenium catalysts were also recognized. The optimal parameters of the scaled-up synthesis together with productivity of catalyst were first established.

Assessment of the Potential and Limitations of Elemental Mass Spectrometry in Life Sciences for Absolute Quantification of Biomolecules Using Generic Standards.

Inductively coupled plasma-mass spectrometry (ICP-MS) has been widely used in Life Sciences for the absolute quantification of biomolecules without specific standards, assuming the same response for generic compounds including complex biomolecules. However, contradictory results have been published on this regard. We present the first critical statistical comparison of the ICP-MS response factors obtained for 14 different relevant S-containing biomolecules (three peptides, four proteins, one amino acid, two cofactors, three polyethylene glycol (PEG) derivatives, and sulfate standard), covering a wide range of hydrophobicities and molecular sizes. Two regular flow nebulizers and a total consumption nebulizer (TCN) were tested. ICP-MS response factors were determined though calibration curves, and isotope dilution analysis was used to normalize the results. No statistical differences have been found for low-molecular-weight biocompounds, PEGs, and nonhydrophobic peptides using any of the nebulizers tested. Interestingly, while statistical differences were still found negligible (96-104%) for the proteins and hydrophobic peptide using the TCN, significantly lower response factors (87-40%) were obtained using regular flow nebulizers. Such differential behavior seems to be related mostly to hydrophobicity and partially to the molecular weight. Findings were validated using IDA in intact and digested bovine serum albumin solutions using the TCN (98 and 100%, respectively) and the concentric nebulizer (73 and 97%, respectively). Additionally, in the case of a phosphoprotein, results were corroborated using the P trace in parallel to the S trace used along the manuscript. This work seems to suggest that ICP-MS operated with regular nebulizers can offer absolute quantification using generic standards for most biomolecules except proteins and hydrophobic peptides.

Multicomponent Alginate‐Derived Hydrogel Microspheres Presenting Hybrid Ionic‐Covalent Network and Drug Eluting Properties

AbstractThe development of multifunctional encapsulation biomaterials could help the translation of cell‐based therapies into standard medical care. One of the major hurdles in the field of encapsulated cell transplantation is the current lack of materials presenting optimal properties, including long term stability, mechanical durability and non‐immunogenic character. Modification of sodium alginate (Na‐alg) with polyethylene glycol (PEG) derivatives, without restricting its gelling abilities, appeared as an efficient strategy to produce dual ionic‐covalent spherical hydrogels with enhanced mechanical performance as well as drug‐eluting microspheres (MS) for the mitigation of inflammatory response after transplantation. In this study, the combination of PEGylated alginates equipped with cross‐reactive functionalities and the anti‐inflammatory drug ketoprofen (KET) resulted in the assembly of multifunctional (MF) hybrid MS, merging the advantages of ionic‐covalent hydrogels with the ability for controlled drug delivery. Physical characterization confirmed their improved mechanical resistance, their higher shape recovery performance and increased stability toward non‐gelling ions, as compared to pure Ca‐alg hydrogels. In vitro release kinetics revealed the controlled and sustained delivery of KET for over two weeks.

Regenerable solid molecular basket sorbents for selective SO2 capture from CO2-rich gas streams

A series of molecular basket sorbents (MBSs) consisting of SBA-15 loaded with ethylene glycol (EG) derivatives and dimethyl sulfoxide (DMSO) are developed and investigated for sulfur dioxide (SO2) capture from industrial tail gas streams. The EG derivatives and DMSO are successfully immobilized on the support via surface interaction with the silanol groups as evidenced by DRIFTS analysis. The mesoporous structure of SBA-15 is preserved after loading with different compounds, with no major morphology changes. The SO2 sorption capacity increases with decreasing the molecular weight of EG derivatives. Furthermore, changing the terminal group of EG derivatives from hydroxyl (-OH) to methoxy (-OCH3) improves SO2 sorption capacity. DMSO-based MBS exhibits much higher SO2 affinity (64 mg-SO2/g-sorb.) than EG-based sorbents (<25 mg-SO2/g-sorb.). DMSO/SBA-15 sorbents are able to selectively capture SO2 in the presence of high CO2 concentration (30 %) with a relative selectivity factor of 120. Pre-saturating the DMSO-based sorbents with water vapor does not affect SO2 sorption capacity, and the sorbents possess good stability and regenerability. Moreover, the spent DMSO/SBA-15 sorbent could be further applied for H2S removal for producing elemental sulfur via Claus reaction between H2S and the adsorbed SO2, providing an environmentally friendly and sustainable way of regenerating the spent DMSO/SBA-15 sorbents.

Exploration of Alternative Scaffolds for P2Y14 Receptor Antagonists Containing a Biaryl Core.

Various heteroaryl and bicyclo-aliphatic analogues of zwitterionic biaryl P2Y14 receptor (P2Y14R) antagonists were synthesized, and affinity was measured in P2Y14R-expressing Chinese hamster ovary cells by flow cytometry. Given this series' low water solubility, various polyethylene glycol derivatives of the distally binding piperidin-4-yl moiety of moderate affinity were synthesized. Rotation of previously identified 1,2,3-triazole attached to the central m-benzoic acid core (25) provided moderate affinity but not indole and benzimidazole substitution of the aryl-triazole. The corresponding P2Y14R region is predicted by homology modeling as a deep, sterically limited hydrophobic pocket, with the outward pointing piperidine moiety being the most flexible. Bicyclic-substituted piperidine ring derivatives of naphthalene antagonist 1, e.g., quinuclidine 17 (MRS4608, IC50 ≈ 20 nM at hP2Y14R/mP2Y14R), or of triazole 2, preserved affinity. Potent antagonists 1, 7a, 17, and 23 (10 mg/kg) protected in an ovalbumin/Aspergillus mouse asthma model, and PEG conjugate 12 reduced chronic pain. Thus, we expanded P2Y14R antagonist structure-activity relationship, introducing diverse physical-chemical properties.

Bioinformatics and Molecular Insights to Anti-Metastasis Activity of Triethylene Glycol Derivatives.

The anti-metastatic and anti-angiogenic activities of triethylene glycol derivatives have been reported. In this study, we investigated their molecular mechanism(s) using bioinformatics and experimental tools. By molecular dynamics analysis, we found that (i) triethylene glycol dimethacrylate (TD-10) and tetraethylene glycol dimethacrylate (TD-11) can act as inhibitors of the catalytic domain of matrix metalloproteinases (MMP-2, MMP-7 and MMP-9) by binding to the S1’ pocket of MMP-2 and MMP-9 and the catalytic Zn ion binding site of MMP-7, and that (ii) TD-11 can cause local disruption of the secondary structure of vascular endothelial growth factor A (VEGFA) dimer and exhibit stable interaction at the binding interface of VEGFA receptor R1 complex. Cell-culture-based in vitro experiments showed anti-metastatic phenotypes as seen in migration and invasion assays in cancer cells by both TD-10 and TD-11. Underlying biochemical evidence revealed downregulation of VEGF and MMPs at the protein level; MMP-9 was also downregulated at the transcriptional level. By molecular analyses, we demonstrate that TD-10 and TD-11 target stress chaperone mortalin at the transcription and translational level, yielding decreased expression of vimentin, fibronectin and hnRNP-K, and increase in extracellular matrix (ECM) proteins (collagen IV and E-cadherin) endorsing reversal of epithelial–mesenchymal transition (EMT) signaling.

Glycerol to renewable fuel oxygenates. Part II: Gasoline-blending characteristics of glycerol and glycol derivatives with C3-C4 alkyl(idene) substituents

The main physico-chemical features, as well as gasoline blending features of eight diol derivatives (1,3-diisopropyl and 1,3-di-tert-butyl glycerol ethers – di-GIPE and di-GTBE; O-isopropyl and O-tert-butyl solketal ethers – SIPE and STBE; isopropylidene ketals of ethylene and propylene glycol – DMD and TMD; cyclic ketals of glycerol with the methyl ethyl ketone and the methyl isobutyl ketone – GBK and GHK) have been estimated in order to reveal the relations between the molecular structures of the compounds and their efficiency as the gasoline oxygenated additives. For the oxygenates, the experimental values of the density, the boiling/melting point, the viscosity and the net heat of the combustion have been obtained. The characteristics of the estimated oxygenate-gasoline blends have involved their density, the calorific value, the fractional composition, the saturated vapor pressure, the research octane number and the motor octane numbers (ON), the oxidation stability, the gum content and the pour point. For di-GTBEs, as the most effective octane booster (among the compounds tested), the effect on the gasoline calorific value has been researched in the combination with the antiknock features improvement, which shows the evident advantages over ethanol and MTBE relatively to ΔAKI/ΔNHOC ratio.

Redox-responsive functionalized hydrogel marble for the generation of cellular spheroids

Liquid marbles (LMs) have recently shown a great promise as microbioreactors to construct self-supported aqueous compartments for chemical and biological reactions. However, the evaporation of the inner aqueous liquid core has limited their application, especially in studying cellular functions. Hydrogels are promising scaffolds that provide a spatial environment suitable for three-dimensional cell culture. Here, we describe the fabrication of redox-responsive hydrogel marbles (HMs) as a three-dimensional cell culture platform. The HMs are prepared by introducing an aqueous mixture of a tetra-thiolated polyethylene glycol (PEG) derivative, thiolated gelatin (Gela-SH), horseradish peroxidase, a small phenolic compound, and human hepatocellular carcinoma cells (HepG2) to the inner aqueous phase of LMs. Eventually, HepG2 cells are encapsulated in the HMs then immersed in culture media, where they proliferate and form cellular spheroids. Experimental results show that the Gela-SH concentration strongly influences the physicochemical and microstructure properties of the HMs. After 6 days in culture, the spheroids were recovered from the HMs by degrading the scaffold, and examination showed that they had reached up to about 180μm in diameter depending on the Gela-SH concentration, compared with 60μm in conventional HMs without Gela-SH. After long-term culture (over 12 days), the liver-specific functions (secretion of albumin and urea) and DNA contents of the spheroids cultured in the HMs were elevated compared with those cultured in LMs. These results suggest that the developed HMs can be useful in designing a variety of microbioreactors for tissue engineering applications.

Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation.

Neuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system, and accounts for approximately 15% of all pediatric cancer‐related deaths. As the 5‐y survival rate of patients with high‐risk NB is <50%, novel therapeutic strategies for NB patients are urgently required. Nonaethylene glycol mono(′4‐iodo‐4‐biphenyl)ester (9bw) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria. Although 9bw shows remarkable inhibition of tumor cell growth, the underlying mechanisms remain unclear. Here, we examined the efficacy of 9bw on human NB‐derived cells, and investigated the molecular mechanisms underlying the cytotoxic effects of 9bw on these cells. Our results indicated that 9bw induced cell death in NB cells by decreasing the production of ATP. Metabolome analysis and measurement of oxygen consumption indicated that 9bw markedly suppressed oxidative phosphorylation (OXPHOS). Further analyses indicated that 9bw inhibited the activity of mitochondrial respiratory complex I. Moreover, we showed that 9bw inhibited growth of NB in vivo. Based on the results of the present study, 9bw is a good candidate as a novel agent for treatment of NB.

Unique Behavior of Poly(propylene glycols) Confined within Alumina Templates Having a Nanostructured Interface.

Herein we show that the nanostructured interface obtained via modulation of the pore size has a strong impact on the segmental and chain dynamics of two poly(propylene glycol) (PPG) derivatives with various molecular weights (Mn = 4000 g/mol and Mn = 2000 g/mol). In fact, a significant acceleration of the dynamics was observed for PPG infiltrated into ordinary alumina templates (Dp = 36 nm), while bulklike behavior was found for samples incorporated into membranes of modulated diameter (19 nm < Dp < 28 nm). We demostrated that the modulation-induced roughness reduces surface interactions of polymer chains near the interface with respect to the ones adsorbed to the ordinary nanochannels. Interestingly, this effect is noted despite the enhanced wettability of PPG in the latter system. Consequently, as a result of weaker H-bonding surface interactions, the conformation of segments seems to locally mimic the bulk arrangement, leading to bulklike dynamics, highlighting the crucial impact of the interface on the overall behavior of confined materials.

Radical-Hydroboration-Involved One-Pot Synthesis of Boron-Handled Glycol Derivatives

A one-pot two-step protocol for the direct synthesis of boron-handled glycol derivatives is reported. The procedure starts by an NHC–boryl-radical-promoted regioselective hydroboration of glycol-protected cinnamaldehydes. After that, the reaction mixture is treated with pinacol in the presence of HCl, leading to the direct formation of pinacol boronate handled glycol monoalkyl ethers. In this acid-triggered conversion, a reductive ring-opening of glycol-derived acetal moiety takes place, during which an NHC–borane unit serves as the hydride source.

Catalytic Transesterification Routes to Novel Vinyl Glycolate Derivatives of Polyhydric Alcohols

Methyl vinyl glycolate (methyl 2-hydroxybut-3-enoate, MVG) has recently become obtainable from Sn catalysed cascade reactions of mono- and disaccharides. The chemical structure of MVG present several options for chemical transformations and has great potential as a renewable platform chemical for industrial added-value compounds within e.g. polymer chemistry. Herein, we report a catalytic benign transesterification method for the synthesis of MVG ester derivatives of trimethylolpropane (TMP) and pentaerythritol (PE). The secondary alcohol group of MVG greatly complicates the reaction and requires a highly selective catalyst to direct the reaction towards high conversion while avoiding polymerization. Thus, a range of different catalytic systems, e.g. Candida Antarctica Lipase B (CALB), Bronsted bases/acids, salicylic aldehyde as well as Lewis acids were evaluated for the reaction. Despite the challenges this leads to unique derivatives of TMP and PE with an additional chemical handle compared to classic derivatives like the methacrylate and mercaptopropionate.

Some Guidelines for the Synthesis and Melting Characterization of Azide Poly(ethylene glycol) Derivatives.

We provide fundamental guidelines in the form of a tutorial to be taken into account for the preparation and characterization of a specific class of poly(ethylene glycol) (PEG) derivatives, namely azide-terminated PEGs. Special attention is given to the effect of these chain end groups and their precursors on properties affecting the PEGylation of proteins, nanoparticles and nanostructured surfaces. Notwithstanding the presence of 13C satellite peaks, we show that 1H NMR enables not only the routine quantitative determination of chain-end substitution, but is also a unique method to calculate the absolute number average molecular weight of PEG derivatives. In the use of size exclusion chromatography to get molecular weight distributions, we highlight the importance of distinguishing between eventual secondary reactions involving molecular weight changes and the formation of PEG complexes due to residual amounts of metal cations from reactants. Finally, we show that azide end groups affect PEG melting behavior. In contrast to oxygen-containing end groups, azides do not interact with PEG segments, thus inducing defect formation in the crystal lattice and the reduction of crystal sizes. Melting temperature and degree of crystallinity decrease become especially relevant for PEGs with very low molecular weight, and its comprehension is particularly important for solid-state applications.

Hemolytic and Antimicrobial Activities of a Series of Cationic Amphiphilic Copolymers Comprised of Same Centered Comonomers with Thiazole Moieties and Polyethylene Glycol Derivatives.

A series of well-defined antimicrobial polymers composed of comonomers bearing thiazole ring (2-(((2-(4-methylthiazol-5-yl)ethoxy)carbonyl)oxy)ethyl methacrylate monomer (MTZ)) and non-hemotoxic poly(ethylene glycol) side chains (poly(ethylene glycol) methyl ether methacrylate (PEGMA)) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. By post-polymerization functionalization strategy, polymers were quaternized with either butyl or octyl iodides to result in cationic amphiphilic copolymers incorporating thiazolium groups, thus with variable hydrophobic/hydrophilic balance associated to the length of the alkylating agent. Likewise, the molar percentage of PEGMA was modulated in the copolymers, also affecting the amphiphilicity. The antimicrobial activities of these cationic polymers were determined against Gram-positive and Gram-negative bacteria and fungi. Minimum inhibitory concentration (MIC) was found to be dependent on both length of the alkyl hydrophobic chain and the content of PEGMA in the copolymers. More hydrophobic octylated copolymers were found to be more effective against all tested microorganisms. The incorporation of non-ionic hydrophilic units, PEGMA, reduces the hydrophobicity of the system and the activity is markedly reduced. This effect is dramatic in the case of butylated copolymers, in which the hydrophobic/hydrophilic balance is highly affected. The hemolytic properties of polymers analyzed against human red blood cells were greatly affected by the hydrophobic/hydrophilic balance of the copolymers and the content of PEGMA, which drastically reduces the hemotoxicity. The copolymers containing longer hydrophobic chain, octyl, are much more hemotoxic than their corresponding butylated copolymers.

The Physiology of Sphincter and Dilator Muscles in the Regulation of Intraocular Pressure

Iris is a small pigmented sheet in between cornea and the lens that is constantly bathed in aqueous humor. Two sets of muscles that are opposite in their function constitute the iris (sphincter for contraction, and the dilator for dilation) and these muscles are responsible for maintaining the normal size of the pupil. Thus, their proper functioning is important for iris health. Common manifestations that lead to secondary glaucomatous conditions include iritis, and anterior uveitis. Uveitis, a sight‐threatening emergency is responsible for more than 30,000 legal blinding in the US alone, and it accounts for 10–15% of blindness. The cause of most uveitis cases is idiopathic. Although homocysteine (Hcy), and the high glucose contribute to ocular dysfunction, but the mechanisms are not clear. This study investigated the role of Hcy, and the hyperglycemia (HG), and their contribution to the biology of sphincter, and dilator muscles in the regulation of intraocular pressure (IOP). We hypothesize that metabolic dysregulation of iris muscles during hyperhomocysteinemia (HHcy), and or HG is responsible for ocular hypertension. Therefore, restoration of the iris homeostasis by direct pharmacological intervention (e.g. dilator/constrictor/antioxidants: such as Tropicamide, acetylcholine, sodium nitroprusside, epinephrine, norepinephrine, glycol and atropine derivatives, and hydrogen sulfide donor; GYY 4137) could help modulate the pressure in the eye. When tested, as eye drops, employing Ins2Akita, and CBS+/− strains of mouse models representing HHcy, and HG conditions, the IOP was measured before, and after the application of above agents in treated, and untreated mice groups. Findings reveal that Tropicamide was more effective than others. Some agents, not all, were able to lower IOP significantly in a gender‐specific manner. We are currently dissecting‐out the molecular mechanism(s) that might reveal new therapeutic targets for treating the hypertensive eyes.Interestingly, both strains of the mice also revealed alterations in their retinae that included occlusion of their vessels along with significant thickening of the retinal layers. Our study has a direct clinical significance where dysfunction of the iris muscles alone or in conjunction with retinal‐ischemia may predispose susceptible patients to higher IOP that is responsible for various forms of glaucomatous phenotypes.

A novel and green sulfur fertilizer from CS2 to promote reproductive growth of plants

Carbon disulfide (CS2) is seen an odor-toxic organic sulfur compound, which presents a major impact on global climate change. Therefore, the conversion of CS2 into valuable chemicals is the key to reduce the concentration of CS2 in the atmosphere. On the basis of a CS2 fixation strategy, CS2-storage materials (CS2SMs) are firstly synthesized by the reaction of CS2 with a binary ion-like liquid systems of ethylenediamine (EDA) and ethylene glycol derivatives (EGs) under mild condition. In view of the serious shortage of sulfur fertilizer and its important position in global agricultural production, it is a promising choice to use the CS2SMs as a new type of green sulfur fertilizer to promote the growth of eggplant, tomato, sweet pepper and cucumber. In this work, the influence of CS2SMs on the growth of plants were studied by taking plants irrigated by using various aqueous CS2SMs solutions as experimental groups, and those irrigated by using water and NH4HCO3 as control groups. The experimental results showed that all CS2SMs could promote plant height, stem diameter, root weight, flower bud number and leaf size. Especially, several CS2SMs presented significant influence on fluorescence and fruit number. Further studies showed that the CS2SMs as new energy resources sulfur-containing boosted leaf area, improved root development, enhanced photosynthesis and soil nutrient uptake, and promoted vegetative and reproductive growth of these four types of plants. Thus, this work provided a new strategy for the use of CS2 as an indirect energy source for the experimental four plants.

Targeted nanosystem combined with chemo-photothermal therapy for hepatocellular carcinoma treatment

The multimodal therapies have showed significantly efficacy in clinical tumor treatment. Nanotechnology provides the powerful platform as multifunctional drug delivery system. Herein, graphene oxide (GO) nanosheets were prepared and modified with polyethylene glycol derivatives and lactobionic acid (LA), which improved their biocompatibility. The anticancer drug curcumin (CUR) that possess various biological effects was selected and successfully loaded onto the nanocomposites by π-π stacking. In vitro results showed that the formulation of GO-PEG/LA-CUR has good biosafety and the ability to specifically target hepatocellular carcinoma cells that overexpress asialoglycoprotein receptor (ASGPR). The in vivo experiments also demonstrated excellent biodistribution of GO-PEG/LA-CUR nanocomposites. The tumor growth was significantly inhibited in subcutaneous HCC tumor-bearing mice treated with GO-PEG/LA-CUR after near-infrared (NIR) irradiation, with a tumor inhibition rate of 86 %, demonstrating the synergistic chemo-photothermal therapy (PTT) efficacy. The therapeutic nanocomposites can be a useful PTT-combined platform for the clinical HCC treatment.