Phospholipid Layer Research Articles

Influence of NaCl on the Structure and Dynamics of Phospholipid Layers

We present a structural and dynamical analysis of the influence of NaCl on multilayer stacks of phospholipids on a solid surface. To this end, multilayer stacks of phospholipids (L-α-phosphatidylcholine, abbreviated as SoyPC) are investigated with neutron reflectometry, grazing-incidence small-angle neutron scattering (GISANS) and grazing-incidence neutron-spin echo spectroscopy (GINSES). We show both that the NaCl influence on the structure is predominantly on water-head group interface and also, that the change in dynamics is restricted to an associated change in the inter-plane viscosity. Using this knowledge, it is possible to model the dynamical behavior of a phospholipid membrane in response to a salt concentration of the solvent using only a single parameter, namely the in-plane viscosity. The excellent agreement with our previously published model also strongly supports the existence of a thermally excited surface mode in phospholipid membranes for close-to-physiological conditions.

Selective association of desmin intermediate filaments with a phospholipid layer in droplets

Desmin, an intermediate filament protein expressed in muscle cells, plays a key role in the integrity and regulation of the contractile system. Furthermore, the distribution of desmin in cells and its interplay with plasma and organelle membranes are crucial for cell functions; however, the fundamental properties of lipid-desmin interactions remain unknown. Using a water-in-oil method for a limited space system in vitro, we examined the distribution of desmin in three types of phospholipid droplets: 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dioleoyl-sn-glycero-3-phosphoserine (DOPS). When fluorescent-labeled desmin was observed for 60 min after desmin assembly was initiated by adding 25 mM KCl, desmin accumulated on both the DOPE and DOPS layers; however, it did not accumulate on the DOPC layer of droplets. An increase in salt concentration did not moderate the accumulation. The initial form of either oligomer or mature filament affected the accumulation on each lipid layer. When liposomes were included in the droplets, desmin was associated with DOPE but not on DOPC liposomes. These results suggest that desmin has the potential for association with phospholipids concerning desmin form and lipid shape. The behavior and composition of living membranes may affect the distribution of desmin networks.

Tuning stable noble metal nanoparticles dispersions to moderate their interaction with model membranes

HypothesisThe properties of stable gold (Au) nanoparticle dispersions can be tuned to alter their activity towards biomembrane models. ExperimentsAu nanoparticle coating techniques together with rapid electrochemical screens of a phospholipid layer on fabricated mercury (Hg) on platinum (Pt) electrode have been used to moderate the phospholipid layer activity of Au nanoparticle dispersions. Screening results for Au nanoparticle dispersions were intercalibrated with phospholipid large unilamellar vesicle (LUV) interactions using a carboxyfluorescein (CF) leakage assay. All nanoparticle dispersions were characterised for size, by dynamic light scattering (DLS) and transmission electron microscopy (TEM). FindingsCommercial and high quality home synthesised Au nanoparticle dispersions are phospholipid monolayer active whereas Ag nanoparticle dispersions are not. If Au nanoparticles are coated with a thin layer of Ag then the particle/lipid interaction is suppressed. The electrochemical assays of the lipid layer activity of Au nanoparticle dispersions align with LUV leakage assays of the same. Au nanoparticles of decreasing size and increasing dispersion concentration showed a stronger phospholipid monolayer/bilayer interaction. Treating Au nanoparticles with cell culture medium and incubation of Au nanoparticle dispersions in phosphate buffered saline (PBS) solutions removes their phospholipid layer interaction.

Clinical Features of Post-Parturient Hemoglobinuria in Dairy Cattle and Buffaloes: A Review

Postpartum hemoglobinuria (PPH) is a sporadic noninfectious syndrome which normally seen in bovine around the world. PPH is most commonly affecting high-productive cows and buffaloes during the early pregnancy and early lactation period. PPH stands as a serious threat to the dairy cattle and buffaloes in Afghanistan, Pakistan, and India, affecting a considerable number of animals every year. It is characterized by hemoglobinuria, intravenous hemolysis, severe anemia, and death due to anemia and hypoxia. However, the exact mechanism of the mentioned illness is not completely understood. Lots of comprehensive studies have been done and/or still are in progress in order to find the exact causes of intravascular hemolysis that is responsible for hemoglobinuria in the mentioned disease. But, hypophosphatemia in the high productive milking cows during the early stage of milk production is widely confident to be associated with PPH. In different parts of the world, many risk factors had been reported to be associated with PPH. Decreasing the level of phosphorous in blood serum, interrupted the phospholipid layers of red blood cells resulting in hemoglobinuria, a decrease in milk production, anorexia, and the death of animals in the cause if remained untreated. Urinalysis and hematology findings are the most commonly suitable diagnostic tools for this disease. Lots of studies have been suggesting that injection of sodium acid phosphate along with important minerals and supportive therapy with anti-oxidants can be used as the therapeutic protocol for the management of PPH.

The process for the production of high phospholipid containing eicosanoids and soluble oligopeptides from the <i>Oyster.</i> sp.

Oysters could be found in seashore and estuarine areas and is regarded as a valuable export product with high economic value. In addition, the oysters could serve as an efficient assimilator of nutrients and potential source of polyunsaturated fatty acids (PUFA), mainly omega-3 fatty acids, which have been found to be responsible for a wide array of health benefits. In this paper, we report a process for the production of high phospholipid containing eicosanoids and soluble oligopeptides from the Oyster. sp. This result shows phospholipid layer containing high eicosanoids with 34.4% and soluble oligopeptides containing 8 essential acid amides. 19.53 g histidine per 100 g oligopeptides pointed out that hydrolyzed oysters are highly nutritional and valuable pharmacological products.

A Review on Biochemical and Immunological Biomarkers used for Laboratory Diagnosis of SARS-CoV-2 (COVID -19)

COVID-19 caused by SARS-CoV-2 is considered an emerging disease that results in severe acute respiratory syndrome. Coronaviruses, as single-stranded RNA viruses, have envelope and positive-sense genome. Virion’s nucleocapsid contains genomic RNA and phosphorylated nucleocapsid protein, which is located within the phospholipid layers and is covered with spike proteins. Although considerable research improvements have occurred, the virus origin is yet obscure. There are several factors that contribute to the development of COVID-19, such as mutations, viral loads, and the survival of the virus in the laboratory, or related factors such as age, sex, and immune status. Proper diagnosis of changes in biochemical and immunological factors affecting COVID-19 leads to the rapid detection of this disease. Finding suitable biochemical and immunological biomarkers could help us in early diagnosis and reducing the casualties of this disease. However, further studies for finding a good solution to early diagnosis require a better understanding of the mechanism of action of this virus. In this review, we review the biochemical and immunological biomarkers used for laboratory diagnosis of SARS-CoV-2 (COVID -19).

Interplay of the Assembly Conditions on Drug Transport Mechanisms in Polyelectrolyte Multilayer Films.

The layer-by-layer film deposition is a suitable strategy for the design and functionalization of drug carriers with superior performance, which still lacks information describing the influence of assembly conditions on the mechanisms governing the drug release process. Herein, traditional poly(acrylic acid)/poly(allylamine) polyelectrolyte multilayers (PEM) were explored as a platform to study the influence of the assembly conditions such as pH, drug loading method, and capping layer deposition on the mechanisms that control the release of calcein, the chosen model drug, from PEM. Films with 20–40 bilayers were assembled at pH 4.5 or 8.8, and the drug loading process was carried out during- or post-film assembly. Release data were fitted to three release models, namely, Higuchi, Ritger–Peppas, and Berens–Hopfenberg, to investigate the mechanism governing the drug transport, such as the apparent diffusion and the relaxation time. The postassembly drug loading method leads to a higher drug loading capacity than the during-assembly method, attributed to the washing out of calcein during film assembly steps in the latter method. Higuchi’s and Ritger–Peppas’ model analyses indicate that the release kinetic constant increased with the number of bilayers for the postassembly method. The opposite trend is observed for the during-assembly method. The Berens–Hopfenberg release model enabled the decoupling of each drug transport mechanism’s contribution, indicating the increase of the diffusion contribution with the number of bilayers for the postassembly method at pH 4.5 and the increase of the polymer relaxation contribution for the during-assembly method at pH 8.8. Deborah’s number, which represents the ratio of the polymer relaxation time to the diffusion time, follows the trends observed for the relaxation contribution for the conditions investigated. The deposition of the capping phospholipid layer over the payload also favored the polymer relaxation contribution in the drug release, featuring new strategies to investigate the drug release in PEM.

On the Action of Ozone on Phospholipids, a Model Compound of the External Envelope of Pericapsidic Viruses like Coronavirus. Part 1

ABSTRACT Coronavirus is a virus with an external protective membrane known as pericapsid and composed essentially by a double layer of phospholipids (PPL) and other components. The destabilization or the decomposition of this pericapsid means the certain inactivation of the coronavirus. The purpose of this work is to show that ozone is able to oxidize easily the phospholipids destabilizing the micellar state of phospholipidic model compounds derived from soy lecithin. PPL were ozonized in reversal micelle state in n-hexane and in normal micelle state in aqueous emulsion. The progress of PPL ozonation was followed spectrophotometrically and iodometrically. It was found that in n-hexane PPL ozonides (PPL-O) start to precipitate at O3/PPL = 1.5 molar ratio and the precipitation is complete at a molar ratio = 3, confirming the average presence of three double bonds per PPL molecule. The pseudofirst order kinetics of the reverse micelle destabilization oxidation to PPL-O was determined in the range of 1.98–6.75 × 10−3 s−1. On the other hand, PPL in aqueous medium forms a milky emulsion with the PPL molecules arranged in the micelle. The action of ozone on this emulsion causes the complete destabilization of the micelles due to the oxidation of the unsaturated fatty chains of PPL and at O3/PPL = 3 molar ratio the solution appears completely transparent, i.e. the original micellar state is disappeared at a rate of 3.0 × 10−3 s−1. PPL-O was also studied by FT-IR, DSC and polarimetry. The results derived from the ozonation of PPL model compound may be applied to the PPL double layer of coronavirus pericapsid, confirming the effectiveness of ozone in coronavirus inactivation.

Self-Emergent Protocells Generated in an Aqueous Solution with Binary Macromolecules through Liquid-Liquid Phase Separation.

Recently, liquid–liquid phase separation (LLPS) has attracted considerable attention among researchers in the life sciences as a plausible mechanism for the generation of microstructures inside cells. LLPS occurs through multiple nonspecific interactions and does not always require a lock‐and‐key interaction with a binary macromolecular solution. The remarkable features of LLPS include the non‐uniform localization and concentration of solutes, resulting in the ability to isolate certain chemical systems and thereby parallelize multiple chemical reactions within the limited space of a living cell. We report that, by using the macromolecules, poly(ethylene glycol) (PEG) and dextran, that exhibit LLPS in an aqueous solution, cell‐sized liposomes are spontaneously formed therein in the presence of phospholipids. In this system, LLPS is generated through the depletion effect of macromolecules. The results showed that cell‐like microdroplets entrapping DNA wrapped by a phospholipid layer emerge in a self‐organized manner.

Altering model cell membranes by means of localized magnetic heating

Isolated iron oxide magnetic nanoparticles (MNPs), 12 nm in diameter, coated with oleic acid molecules as capping agents have been deposited by the Langmuir-Blodgett (LB) method onto a model cell membrane incorporating 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and Cholesterol (Chol) in the 1:1 ratio, which was also fabricated by the LB technique. Atomic Force Microscopy (AFM) experiments showed that the application of an alternating magnetic field results in the embedding of the MNPs through the phospholipidic layer. These experimental results reveal that the heating of individual MNPs may induce a local increase in the fluidity of the film with a large control of the spatial and temporal specificity.

Aggregation-Induced Emission of Water-Soluble Tetraphenylethene Derivatives at Polarized Liquid|Liquid Interfaces.

Aggregation-induced emission (AIE) behavior of water-soluble tetraphenylethene (TPE) derivatives bearing carboxy and sulfo groups was studied at polarized liquid|liquid interfaces. The aggregation behavior of TPE derivatives in solution and at the water|1,2-dichloroethane (DCE) interface was highly dependent on their ionizable functional groups. Spectroelectrochemical analysis elucidated that the TPE derivatives were transferred across the interface accompanied by the adsorption process at the interface. The ion transfer and interfacial AIE features of TPEs responded reversibly to the externally applied potential, indicating no rigid crystalline structure formation in the interfacial region. The red shift measured in intense interfacial emission spectra demonstrated that the carboxylate derivatives formed their J-aggregates specifically at the polarized water|DCE interface, while the aggregation processes with distinguishable emission properties took place in both the interfacial region and organic solution in the sulfonate derivative system. The AIE features were also investigated at a glycerophospholipid-adsorbed interface as a model of the biomembrane surface. The aggregation process of TPE derivatives was significantly modified through the interaction with phospholipid layers which stimulate the interfacial AIE process of tetra-anionic TPEs.

Rational engineering of chromic material as near-infrared ratiometric fluorescent nanosensor for H2S monitoring in real food samples

Food pollution has aroused increasing public health concerns and poses a huge medical and financial burden today. Here, we report a facile one-pot synthesis of hydrogen sulfide (H2S)-responsive near-infrared (NIR) ratiometric fluorescent nanoprobe NIR775/Cy7Cl@HyNPs by encapsulating H2S-sensitive organic chromic cyanine dye Cy7Cl and H2S-inert fluorophore NIR775 into an amphiphilic phospholipid polymer. Because of the confinement effect of phospholipid layer, the loaded NIR775 and Cy7Cl could be brought in close proximity for fluorescence resonance energy transfer (FRET) to occur, leading to single emission of Cy7Cl at ∼ 810 nm inside nanoprobe NIR775/Cy7Cl@HyNPs. However, with the introduction of H2S, the FRET process from NIR775 to Cy7Cl is disrupted due to the stimuli-responsive chromic behavior as a result of H2S-triggered nucleophilic, leading to restoring of the fluorescence emission of NIR775 at ∼ 778 nm companied by a remarkable fluorescence decrease of Cy7Cl at ∼ 810 nm, thereby enabling nanoprobe NIR775/Cy7Cl@HyNPs to show a NIR ratiometric response toward H2S. As expected, the nanoprobe NIR775/Cy7Cl@HyNPs exhibits a prominent practicability to precisely report the levels of H2S in actual food mediums with a wide linear range of 0.0367–120.0 μM, a satisfactory limit detection of 11.0 nM, as well as an excellent specificity over other sulfur-containing substances (e.g. biothiols). This study emphasizes the promise for utilizing switchable chromic materials to develop a new category of NIR ratiometric fluorescent nanosensors facilitating accurate and reliable measurement in actual food and agriculture-related systems without any pretreatments, which is of great significance for safeguarding food safety and human health.

Lipid droplets formation and their effects on phosphatidylinositol level in yeasts

Lipid droplets (LDs) are conserved specialized organelles that are surrounded by a single phospholipid layer, enclosing neutral lipids in form of triacylglycerol (TAG) and/or sterol ester. They are formed at the endoplasmic reticulum (ER), and stay connected to it in the yeast cell. These LDs mainly play major roles in lipid storage and homeostasis. Moreover, they have several functions in the yeast cell including; protein degradation, protein glycosylation, response to ER stress, in addition to providing substrate for energy metabolism and for membrane synthesis. In general, TAG and phosphatidylinositol (PI) synthesis share the same precursor; phosphatidic acid (PA), which controls their level. By the actions of lipases, phosphatases and/or kinases; one can act as a precursor for another, thus explaining the reason of their inverse correlation. TAG lipolysis is catalyzed by TAG lipases producing fatty acids and diacylglycerol (DAG). The DAG produced from lipolysis is phosphorylated by diacylglycerol kinase (Dgk1) to form PA. On the other hand, PA is a cell signaling molecule and once increased, it upregulates cytidine diphosphate diacylglycerol (CDP-DAG) pathway for the PI synthesis. Major TAG lipases are mainly localized in LD, whereas minor amounts of them are localized in ER. Once DAG is produced inside the LD, it is transferred to the ER by inheritance cortical ER protein, Ice2, for further reactions. The TAG and PI levels are also controlled by transcriptional regulation in response to inositol and zinc. The aim of this study was to clarify how LDs regulate lipid homeostasis in the yeast cell, and particularly focuses on the balance between TAG and PI.

Dual-encapsulated biodegradable 3D scaffold from liposome and waterborne polyurethane for local drug control release in breast cancer therapy

Compared with the traditional chemotherapy by injection, local release of drugs in the lesion area is a more efficient and less harmful treatment for solid tumors. However, the selection of appropriate drug carrier and controlled release of chemotherapy drugs are still great challenges. Herein, a kind of dual-encapsulated three-dimensional (3D) scaffold is designed for local drug release via blending the paclitaxel (PTX) loaded phospholipid liposomes with waterborne polyurethane (PU) by freeze-drying. The controlled release of paclitaxel is carried out through two simultaneous procedures. First, liposomes encapsulated in polyurethane scaffold can slowly release by water absorption and degradation of polyurethane. Then paclitaxel encapsulated in liposomes can also be released into water. Compared with the polyurethane scaffold which directly encapsulated paclitaxel, dual-encapsulated scaffold has slower initial release amount and maintain higher concentration of paclitaxel in later stage. Moreover, the protection of the phospholipid layer can prevent paclitaxel from being quickly decomposed and cleared, which could greatly improve the bioavailability and therapeutic effect of paclitaxel. Cell experiment results can be seen that dual-encapsulated scaffold not only has higher inhibition rate to the breast cancer MCF7 cells, but also has less damage to normal tissue cells. It provides a more effective platform for the local drug therapy in the treatment of tumors.

Characterization of pH-Responsible Polymer Nano-Film Synthesized on Self-Assembled Phospholipid Layer Fabricated by Plasma-Assisted Method

Characterization of pH-Responsible Polymer Nano-Film Synthesized on Self-Assembled Phospholipid Layer Fabricated by Plasma-Assisted Method

Pathogenic roles and coping strategies of bacterial outer membrane vesicles in sepsis

<p indent="0mm">Sepsis is a life-threatening disease that characterized by systemic inflammatory response and multiple organ dysfunction and mostly caused by Gram-negative bacterial infections. Outer membrane vesicles (OMVs) are multifunctional spherical structures <sc>(10−300 nm)</sc> released from outer membrane of Gram-negative bacteria. Usually, OMVs carry a variety of virulence factors and pathogen-associated molecular patterns (PAMPs), such as toxins, digestive enzymes, lipopolysaccharide (LPS), peptidoglycan, bacterial DNA, etc. Roles of OMVs in bacterial survival include nutrient acquisition, bacterial biofilm formation, antibiotic resistance delivery, and killing of competing microbes. In the pathogenesis of sepsis, OMVs have versatile effects on host cells (such as epithelial cells, immune cells, endothelial cells and platelets, etc.), causing the immune response out of control and the positive feedback loop of inflammation and coagulation formed, which ultimately leading to the systemic inflammatory response and multiple organ dysfunction. Pathogenic effects of OMVs are versatile, including adhesion of host cells, delivery of virulence factors and PAMPs, promotion of inflammatory and immune responses, and facilitation of bacteria survival in the host. Moreover, the main mechanism of bacterial OMVs invading host cells and causing sepsis is related to the recognition of their carried PAMPs with pattern recognition receptors (PRRs) of host cells, including Toll-like receptors (TLRs) on the surface of cell membrane, NOD-like Receptors (NLRs) and cysteinyl aspartate specific proteinases (Caspases) in the cytoplasm. Here, we will briefly introduce the structure composition, biosynthesis and functions of OMVs, particularly focuses on the pathogenic roles of OMVs in the occurrence of sepsis. In addition, the coping strategies of bacterial OMVs in sepsis have been recently investigated since OMVs can carry and transmit a variety of virulence factors. Firstly, OMVs vaccines can prevent the bacterial infection and reduce the OMVs production from the source. Secondly, therapeutic molecules, such as antimicrobial peptides and polymyxin B, can target LPS directly, the common toxic component of bacterial out membranes, and other drugs using TLR4 and Caspase-4/5/11 as targets, also have therapeutic potential to block the inflammatory pathways activated by LPS. Recently, the new drug screening system was established based on bacterial OMVs directly. The treatment effects of the existing drugs for sepsis, including blocking the release of inflammatory factors induced by OMVs, and alleviating the clinical symptoms of sepsis, were reevaluated. Cationic antimicrobial polymers could adsorb the anionic groups of bacterial membrane through the electrostatic interaction, followed by inserting the phospholipid bilayer to destroy the integrity of bacterial membrane and ultimately kill bacteria. Based on the outer membrane structure characteristics of bacterial OMVs (the outmost LPS with more negative charges, toxic protein components, and the inner phospholipid layer with hydrophobicity), the development of cationic antibacterial materials with the integrated function of adsorption and removal of OMVs is feasible to prevent sepsis and other bacterial infection related diseases. Recently, our team designed and synthesized a series of cationic antibacterial polymers, and observed the adsorption capacity of different polymer surfaces to the OMVs of <italic>Pseudomonas aeruginosa</italic> by electron microscopy. The results confirmed that both the cationic polymer membrane and the cation-modified polyurethane foam could adsorb the OMVs. However, the antimicrobial polymers have the possibility to stimulate the release of bacterial OMVs. Therefore, the simultaneous effects of cationic polymers with antimicrobial activities need to be investigated on the release and removal of OMVs in future studies. This review briefly introduces the structural composition, biosynthesis and functions of OMVs, particularly focuses on the pathogenic roles of OMVs in the occurrence of sepsis, and the corresponding coping strategies for the clinical prevention and treatment of sepsis.

Surface Alterations to Impart Antiviral Properties to Combat COVID-19 Transmission.

A global epidemic caused by highly transmittable COVID-19 is causing severe loss of human life. In this study, two aspects of reducing transmission of COVID-19 virus, due to surface contact, are discussed: first refers to the effect of nanocarbon fullerene C60 coating on surface, that causes lipid peroxidation on the phospholipid layer present in the outer envelope of COVID-19; the second aspect refers to creating hydrophobic surfaces by texturing them, so that the contact area between virus and surface is minimized due to the presence of entrapped air between the topographies. These can be similar to micro-/nano-multiscale textured surfaces that have anti-biofouling properties. Fullerene-coated surfaces can be seen as a possible solution to decrease the adhesion of virus on the surface, as they will be hydrophobic as well as toxic to the envelope.

Control of Director Fields in Phospholipid-Coated Liquid Crystal Droplets.

In liquid crystal (LC) droplets, small changes in surface anchoring energy can produce large changes in the director field which result in readily detectable optical effects. This makes them attractive for use as biosensors. Coating LC droplets with a phospholipid monolayer provides a bridge between the hydrophobic world of LCs and the water-based world of biology and makes it possible to incorporate naturally occurring biosensor systems. However, phospholipids promote strong perpendicular (homeotropic) anchoring that can inhibit switching of the director field. We show that the tendency for phospholipid layers to promote perpendicular anchoring can be suppressed by using synthetic phospholipids in which the acyl chains are terminated with bulky tert-butyl or ferrocenyl groups; the larger these end-group(s), the less likely the system is to be perpendicular/radial. Additionally, the droplet director field is found to be dependent on the nature of the LC, particularly its intrinsic surface properties, but not (apparently) on the sign of the dielectric anisotropy, the proximity to the melting/isotropic phase transition, the surface tension (in air), or the values of the Frank elastic constants.

Study of cytotoxicity performance of carbon nanohorns by method of spin probes

The effects of as-produced and treated by HNO3(3M) carbon nanohorns on the microviscosity of rat erythrocyte membranes and the viscosity of the water-containing plasma protein matrix were investigated by the method of spin probes. Addition of nanohorns at the concentration of 100 μg/ml to a suspension of erythrocytes led to an increase in membrane microviscosity during 4 h (about 60% effect). In addition, it was shown that nanohorns also induced an increased polarity of the microenvironment for lipophilic probes in the outer layer of membrane phospholipids, as well as disorders in erythrocytes membranes. Addition of nanohorns to plasma led to a little decrease in the viscosity of water and protein matrix, apparently, due to its partial destruction, impacting especially albumin. Pristine and treated by HNO3(3M) acid nanohorns was found more cytotoxic than nanoparticles of oxidized graphene, and significantly less than carbon nanotubes, which are known to dramatically increase the microviscosity of the membranes of erythrocytes and disrupt their integrity.

Phospholipid-Decorated Glycogen Nanoparticles for Stimuli-Responsive Drug Release and Synergetic Chemophotothermal Therapy of Hepatocellular Carcinoma.

Dendritic macromolecules are potential candidates for nanomedical application. Herein, glycogen, the natural hyperbranched polysaccharide with favorable biocompatibility, is explored as an effective drug vehicle for treating liver cancer. In this system, glycogen is oxidized and conjugated with cancer drugs through a disulfide link, followed by in situ loading of polypyrrole nanoparticles and then coated with functional phospholipids to form the desired system, Gly-ss-DOX@ppy@Lipid-RGD. The phospholipid layer has good cell affinity and can assist the system to penetrate into cells smoothly. Additionally, combined with the "fusion targeting" of glycogen and the active targeting effect of RGD toward liver cancer cells, Gly-ss-DOX@ppy@Lipid-RGD presents efficient specificity and enrichment of hepatocellular carcinoma. Owing to the glutathione-triggered cleavage of disulfide linkers, Gly-ss-DOX@ppy@Lipid-RGD can controllably release drugs to induce cell nucleus damage. Meanwhile, the polypyrrole nanoparticles can absorb near-infrared light and radiate heat energy within tumors. Besides enhancing drug release, the heat can also provide photothermal treatment for tumors. As proved by in vitro and in vivo experiments, Gly-ss-DOX@ppy@Lipid-RGD is a remarkable candidate for synergistic chemophotothermal therapy with high anticancer therapeutic activity and reduced systematic toxicity, efficiently suppressing tumor growth. All results demonstrate that glycogen nanoparticles are expected to be a new building block for accurate hepatocellular carcinoma treatment.