A modular chemoenzymatic cascade strategy for the structure-customized assembly of ganglioside analogs.

Gangliosides play vital biological regulatory roles and are associated with neurological system diseases, malignancies, and immune deficiencies. They have received extensive attention in developing targeted drugs and diagnostic markers. However, it is difficult to obtain enough structurally defined gangliosides and analogs especially at an industrial-relevant scale, which prevent exploring structure-activity relationships and identifying drug ingredients. Here, we report a highly modular chemoenzymatic cascade assembly (MOCECA) strategy for customized and large-scale synthesis of ganglioside analogs with various glycan and ceramide epitopes. We typically accessed five gangliosides with therapeutic promising and systematically prepared ten GM1 analogs with diverse ceramides. Through further process amplification, we achieved industrial production of ganglioside GM1 in the form of modular assembly at hectogram scale. Using MOCECA-synthesized GM1 analogs, we found unique ceramide modifications on GM1 could enhance the ability to promote neurite outgrowth. By comparing the structures with synthetic analogs, we further resolved the problem of contradicting descriptions for GM1 components in different pharmaceutical documents by reinterpreting the exact two-component structures of commercialized GM1 drugs. Because of its applicability and stability, the MOCECA strategy can be extended to prepare other glycosphingolipid structures, which may pave the way for developing new glycolipid drugs.

Pathophysiological roles and applications of glycosphingolipids in the diagnosis and treatment of cancer diseases.

Glycosphingolipids (GSLs) are major amphiphilic glycolipids present on the surface of living cell membranes. They have important biological functions, including maintaining plasma membrane stability, regulating signal transduction, and mediating cell recognition and adhesion. Specific GSLs and related enzymes are abnormally expressed in many cancer diseases and affect the malignant characteristics of tumors. The regulatory roles of GSLs in signaling pathways suggest that they are involved in tumor pathogenesis. GSLs have therefore been widely studied as diagnostic markers of cancer diseases and important targets of immunotherapy. This review describes the tumor-related biological functions of GSLs and systematically introduces recent progress in using diverse GSLs and related enzymes to diagnose and treat tumor diseases. Development of drugs and biomarkers for personalized cancer therapy based on GSL structure is also discussed. These advances, combined with recent progress in the preparation of GSLs derivatives through synthetic biology technologies, suggest a strong future for the use of customized GSL libraries in treating human diseases.

Tropheryma whipplei-induced plastic bronchitis in children: a case report.

This article reports a case of a 7-year-old child with severe pneumonia whose chest CT showed pulmonary consolidation, and bronchoscopy revealed plastic bronchitis. The metagenomic Next-Generation Sequencing (NGS) of the pulmonary lavage fluid suggested the infection of Tropheryma whipplei (T whipplei). The patient was treated with bronchial lavage to remove sputum plugs, intravenous azithromycin, and piperacillin-tazobactam and was discharged after eight days of hospitalization without any recurrence during follow-up. This article aims to raise clinical awareness of T whipplei infection and suggests that NGS for rare pathogens should be performed early for unexplained plastic bronchitis.

Design, synthesis and neurite outgrowth activity of novel ganglioside GM1 derivatives by remodeling of the fatty acid moiety.

Ganglioside GM1 is a glycosphingolipid found on mammalian cell membranes, and it is involved in ischemic encephalopathy, spinal cord injury and neurodegenerative diseases. Fatty acids, as a structure module of GM1, have been reported to affect its physiological function and neurite growth activity. Due to the limitation of preparation methods, the function of GM1 derivatives containing different fatty acids in nerve cells has not been systematically studied. To discover novel GM1 derivatives as nerve growth-promoting agents, we developed an efficient SA_SCDase enzymatic synthetic system of GM1 derivatives, yielding twenty GM1 derivatives with unsaturated fatty acid chains in high total yields (16-67%). Subsequently, the neurite outgrowth activities of GM1 derivatives were assessed on Neuro2a Cells. Among all the GM1 derivatives, GM1 (d18:1/C16:1) induced demonstrably neurite outgrowth activity. The subsequent RNA-sequencing (RNA-seq) and Western blot analysis was then performed and indicated that the mechanism of nerve cells growth involved cholesterol biosynthesis regulation by up-regulating SREBP2 expression or ERBB4 phosphorylation to activate the PI3K-mTOR pathway.

Effect of Vitamin D Combined with Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency.

Objective: Growth hormone deficiency (GHD) refers to the complete or partial lack of pituitary growth hormone synthesis and secretion. This study is aimed at investigating the efficacy of vitamin D and recombinant human growth hormone (rhGH) in children with GHD. Methods: A total of 100 children with GHD at our hospital were included between 1st January 2018 and 31st October 2020. The patients were divided into a study group (n = 70, received vitamin D combined with rhGH) and a control group (n = 30, received rhGH). The growth and development (bone age, growth rate, and height), bone metabolism (bone alkaline phosphatase (BAP), ß-collagen degradation product (ß-CTX), osteocalcin (OC), and amino-terminal propeptide type I procollagen (PINP)), insulin-like growth factor 1 (IGF-1), ghrelin, and adverse reactions in the two groups were measured before and 12 months after treatment. Results: There were no significant differences in the bone age, growth rate, and height between the two groups before treatment. After 12 months of treatment, the bone age, growth rate, and height of the study group were significantly higher than those of the control group. After 12 months of treatment, the levels of serum BAP, PINP, and OC in the study group were significantly higher than those in the control group, while the levels of ß-CTX in the study group were significantly lower than those in the control group. The serum IGF-1 level in the study group was significantly higher than that in the control group, while the ghrelin level in the study group was lower. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion: Combined rhGH and vitamin D treatment can promote growth and development, improve bone metabolism, and regulate IGF-1 and ghrelin levels.

A regulatory GhBPE-GhPRGL module maintains ray petal length in Gerbera hybrida.

The molecular mechanism regulating petal length in flowers is not well understood. Here we used transient transformation assays to confirm that GhPRGL (proline-rich and GASA-like)-a GASA (gibberellic acid [GA] stimulated in Arabidopsis) family gene-promotes the elongation of ray petals in gerbera (Gerbera hybrida). Yeast one-hybrid screening assay identified a bHLH transcription factor of the jasmonic acid (JA) signaling pathway, here named GhBPE (BIGPETAL), which binds to the GhPRGL promoter and represses its expression, resulting in a phenotype of shortened ray petal length when GhBPE is overexpressed. Further, the joint response to JA and GA of GhBPE and GhPRGL, together with their complementary expression profiles in the early stage of petal growth, suggests a novel GhBPE-GhPRGL module that controls the size of ray petals. GhPRGL promotes ray petal elongation in its early stage especially, while GhBPE inhibits ray petal elongation particularly in the late stage by inhibiting the expression of GhPRGL. JA and GA operate in concert to regulate the expression of GhBPE and GhPRGL genes, providing a regulatory mechanism by which ray petals could grow to a fixed length in gerbera species.

Association of Mycoplasma pneumoniae coinfection with adenovirus pneumonia severity in children.

Between the winter of 2018 and the end of 2019, there has been an epidemic of adenovirus infection in southern China, including Zhejiang Province. The number of children suffering from adenovirus pneumonia (AP) has significantly increased. AP can be accompanied by Mycoplasma pneumoniae in children. This study aimed to investigate the association of M. pneumoniae and identify the risk factors for coinfection on hospitalized patients with AP. The patients were classified into two groups by etiologic analysis (single AP and AP with M. pneumoniae coinfection groups). The clinical manifestations, clinical medication, and laboratory and imaging findings of the two groups were compared and analyzed. The coinfection group (n = 125) had a significantly longer duration of fever than the single AP group (n = 171; P = 0.03). Shortness of breath (P = 0.023) and pulmonary imaging findings, such as pulmonary consolidation, atelectasis, pleural effusion, and multilobe lesions (P < 0.05), were more common in the coinfection group. The patients with coinfection had more severe symptoms, significantly longer hospitalization time and an increased proportion of using glucocorticoids and/or immunoglobulin needing oxygen inhalation (P < 0.05). The incidence of AP with M. pneumoniae coinfection is high. The prolonged fever duration and pulmonary imaging findings could be used as prediction factors to predict M. pneumoniae coinfection in children with AP. Patients with AP coinfected with MP may easily develop severe illness. Hence, a reasonable change in the treatment is necessary.

Comprehensive expression profiles and bioinformatics analysis reveal special circular RNA expression and potential predictability in the peripheral blood of humans with idiopathic membranous nephropathy.

The etiology of idiopathic membranous nephropathy (IMN) is considered to be closely associated with immunoregulation and genetic factors. Circular RNAs (circRNAs) have been found to regulate gene expression in various organisms, and to play an important role in multiple physiological and pathological processes, which may be involved in the pathogenesis of IMN. The purpose of the present study was to investigate the potential relationship between circRNAs in peripheral blood and disease. The diagnoses of IMN were confirmed using electron microscopy and immunofluorescence. Total RNA was isolated and microarray analysis was used to detect the expression levels of circRNAs in the peripheral blood of patients with IMN and in normal subjects. Selected genes from the microarray were selected and verified by reverse transcription­quantitative (RT­q)PCR. Bioinformatics tools were applied for further functional evaluation, and the potential disease predictability of circRNAs was determined using receiver­operating characteristic (ROC) curves. The results showed that a total of 955 differentially expressed circRNAs were found in blood samples, 645 of which were upregulated and 310 which were downregulated. In total, five candidate circRNAs were validated using RT­qPCR analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified numerous types of target genes and their corresponding microRNAs (miRNAs). The miRNAs identified were involved in biological processes and enriched in multiple important pathways, including the mitogen­activated protein kinase, transforming growth factor­ß and Ras signaling pathways. The levels of circ_101319 were significantly higher (P<0.001) and exhibited promising diagnostic value in patients with IMN (area under ROC =0.89). The co­expression network constructed for circ_101319 indicated that it may be associated with membranous nephropathy­related pathways by mediating miRNAs. In conclusion, the present study revealed the expression and functional profile of differentially expressed circRNAs in the peripheral blood of patients with IMN, and provided new perspectives to predict and elucidate the development of IMN.

Preparation, intestinal segment stability, and mucoadhesion properties of novel thymopentin-loaded chitosan derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles.

BACKGROUND: In order to develop a promising carrier for the oral delivery of proteins and peptide drugs, a novel bioadhesive nanocarrier of chitosan (CTS) derivatives coated with poly (n-butyl) cyanoacrylate nanoparticles (PBCA-NPs) was prepared in this study. METHODS: Three different thymopentin (TP5)-loaded nanoparticles were prepared in the present study. TP5-PBCA-NPs were developed by modifying an emulsion polymerization method, and CTS and chitosan-glutathione (CG) derivative-coated PBCA nanoparticles were obtained from the electrostatic interactions between CTS or CG with negatively charged PBCA nanoparticles. RESULTS: The particle sizes of TP5-PBCA-NPs, TP5-CTS-PBCA-NPs, and TP5-CG-PBCA-NPs were 212.3±6.9, 274.6±8.2, and 310.4±7.5 nm, respectively, while the respective zeta potentials were -22.6±0.76, 23.3±1.2, and 34.6±1.6 mV with encapsulation efficiencies of 79.37%±2.15%, 74.21%±2.13%, and 72.65%±1.48%, respectively. An everted intestinal ring method indicated that drug stability was remarkably improved after incorporation into the nanoparticles, especially the CG-coated nanoparticles. The mucus layer retention rates for CTS- and CG-coated nanoparticles were 1.43 and 1.83 times that of the uncoated nanoparticles, respectively, using ex vivo mucosa. The in vivo mucoadhesion study illustrated that the transfer of uncoated PBCA-NPs from the stomach to the intestine was faster than that of CTS-PBCA-NPs and CG-PBCA-NPs, while the CG-PBCA-NPs presented the best intestinal retentive characteristic. CONCLUSION: In summary, this study demonstrated the feasibility and benefit of orally delivering peptide drugs using novel CTS derivative-coated nanoparticles with optimal stability and bioadhesive properties.

A Mini Zinc-Finger Protein (MIF) from Gerbera hybrida Activates the GASA Protein Family Gene, GEG, to Inhibit Ray Petal Elongation.

Petal appearance is an important horticultural trail that is generally used to evaluate the ornamental value of plants. However, knowledge of the molecular regulation of petal growth is mostly derived from analyses of Arabidopsis thaliana, and relatively little is known about this process in ornamental plants. Previously, GEG (Gerbera hybrida homolog of the gibberellin [GA]-stimulated transcript 1 [GAST1] from tomato), a gene from the GA stimulated Arabidopsis (GASA) family, was reported to be an inhibitor of ray petal growth in the ornamental species, G. hybrida. To explore the molecular regulatory mechanism of GEG in petal growth inhibition, a mini zinc-finger protein (MIF) was identified using yeast one-hybrid (Y1H) screen. The direct binding of GhMIF to the GEG promoter was verified by using an electrophoretic mobility shift assay and a dual-luciferase assay. A yeast two-hybrid (Y2H) revealed that GhMIF acts as a transcriptional activator. Transient transformation assay indicated that GhMIF is involved in inhibiting ray petal elongation by activating the expression of GEG. Spatiotemporal expression analyses and hormone treatment assay showed that the expression of GhMIF and GEG is coordinated during petal development. Taken together, these results suggest that GhMIF acts as a direct transcriptional activator of GEG, a gene from the GASA protein family to regulate the petal elongation.

BioGPS: building your own mash-up of gene annotations and expression profiles.

BioGPS (http://biogps.org) is a centralized gene-annotation portal that enables researchers to access distributed gene annotation resources. This article focuses on the updates to BioGPS since our last paper (2013 database issue). The unique features of BioGPS, compared to those of other gene portals, are its community extensibility and user customizability. Users contribute the gene-specific resources accessible from BioGPS ('plugins'), which helps ensure that the resource collection is always up-to-date and that it will continue expanding over time (since the 2013 paper, 162 resources have been added, for a 34% increase in the number of resources available). BioGPS users can create their own collections of relevant plugins and save them as customized gene-report pages or 'layouts' (since the 2013 paper, 488 user-created layouts have been added, for a 22% increase in the number of layouts). In addition, we recently updated the most popular plugin, the 'Gene expression/activity chart', to include ∼ 6000 datasets (from ∼ 2000 datasets) and we enhanced user interactivity. We also added a new 'gene list' feature that allows users to save query results for future reference.

[Research progress of in vitro and in vivo anti-tumor effects and formulation of bufalin].

Bufalin is an active compound of the traditional Chinese medicine Chansu, which exhibits significant anti-tumor activities in many solid tumors and leukemia cell lines. Bufalin could introduce apoptosis, reverse drug-resistance, and prevent migration and invasion of tumor cells. This paper reviewed the latest research progress of the in vitro and in vivo anti-tumor effect and mechanism of bufalin on a series of cancers, such as hepatocellular carcinoma, lung cancer, colon cancer, gastric cancer, leukemia, bladder cancer, and its formulation study is also summarized for the reference of its further study and application.

[Recent development of natural and reconstituted lipoprotein based nano drug delivery vehicles].

Lipoproteins are biological lipids carriers. The natural and reconstituted lipoprotein based drug delivery systems have been extensively developed in recent years. This article reviews the development of natural and reconstituted low-density lipoprotein and high-density lipoprotein based vehicles in the antitumor area.

Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases.

As a class of important endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, microRNAs (miRNAs) play a critical role in many physiological and pathological processes. It is believed that miRNAs contribute to the development, differentiation, and synaptic plasticity of the neurons, and their dysregulation has been linked to a series of diseases. MiRNAs exist in the tissues and as circulating miRNAs in several body fluids, including plasma or serum, cerebrospinal fluid, urine, and saliva. There are significant differences between the circulating miRNA expression profiles of healthy individuals and those of patients. Consequently, circulating miRNAs are likely to become a novel class of noninvasive and sensitive biomarkers. Although little is known about the origin and functions of circulating miRNAs at present, their roles in the clinical diagnosis and prognosis of diseases make them attractive markers, particularly for tumors and cardiovascular diseases. Until now, however, there have been limited data regarding the roles of circulating miRNAs in central nervous system (CNS) diseases. This review focuses on the characteristics of circulating miRNAs and their values as potential biomarkers in CNS diseases, particularly in Alzheimer's disease, Huntington's disease, multiple sclerosis, schizophrenia, and bipolar disorder.

Sphingomonas ginsenosidivorax sp. nov., with the ability to transform ginsenosides.

A Gram-negative, strictly aerobic, non-motile, non-spore-forming and rod-shaped bacterial strain designated KHI67(T) was isolated from sediment of the Gapcheon River in South Korea and its taxonomic position was investigated by using a polyphasic approach. Strain KHI67(T) was observed to grow optimally at 25-30 °C and at pH 7.0 on nutrient and R2A agar. On the basis of 16S rRNA gene sequence similarity, strain KHI67(T) was shown to belong to the family Sphingomonadaceae and was related to Sphingomonas faeni MA-olki(T) (97.6 % sequence similarity), Sphingomonas aerolata NW12(T) (97.5 %) and Sphingomonas aurantiaca MA101b(T) (97.3 %). The G + C content of the genomic DNA was determined to be 65.6 %. The major ubiquinone was found to be Q-10, the major polyamine was identified as homospermidine and the major fatty acids identified were summed feature 8 (comprising C18:1 ω7c/ω6c; 37.0 %), C16:0 (13.0 %), summed feature 3 (comprising C16:1 ω7c/C16:1 ω6c; 12.8 %) and C14:0 2OH (9.3 %). DNA and chemotaxonomic data supported the affiliation of strain KHI67(T) to the genus Sphingomonas. The DNA-DNA relatedness values between strain KHI67(T) and its closest phylogenetic neighbours were below 15 %. Strain KHI67(T) could be differentiated genotypically and phenotypically from the recognised species of the genus Sphingomonas. The isolate therefore represents a novel species, for which the name Sphingomonas ginsenosidivorax sp. nov. is proposed, with the type strain KHI67(T) (=KACC 14951(T) = JCM 17076(T) = LMG 25801(T)).

Kinetics of a cloned special ginsenosidase hydrolyzing 3-O-glucoside of multi-protopanaxadiol-type ginsenosides, named ginsenosidase type III.

In this paper, the kinetics of a cloned special glucosidase, named ginsenosidase type III hydrolyzing 3-O-glucoside of multi-protopanaxadiol (PPD)-type ginsenosides, were investigated. The gene (bgpA) encoding this enzyme was cloned from a Terrabacter ginsenosidimutans strain and then expressed in E. coli cells. Ginsenosidase type III was able to hydrolyze 3-O-glucoside of multi-PPD-type ginsenosides. For instance, it was able to hydrolyze the 3-O-ß-D-(1-->2)-glucopyranosyl of Rb1 to gypenoside XVII, and then to further hydrolyze the 3-O-ß-D-glucopyranosyl of gypenoside XVII to gypenoside LXXV. Similarly, the enzyme could hydrolyze the glucopyranosyls linked to the 3-O- position of Rb2, Rc, Rd, Rb3, and Rg3. With a larger enzyme reaction Km value, there was a slower enzyme reaction speed; and the larger the enzyme reaction Vmax value, the faster the enzyme reaction speed was. The Km values from small to large were 3.85 mM for Rc, 4.08 mM for Rb1, 8.85 mM for Rb3, 9.09 mM for Rb2, 9.70 mM for Rg3(S), 11.4 mM for Rd and 12.9 mM for F2; and Vmax value from large to small was 23.2 mM/h for Rc, 16.6 mM/h for Rb1, 14.6 mM/h for Rb3, 14.3 mM/h for Rb2, 1.81mM/h for Rg3(S), 1.40 mM/h for Rd, and 0.41 mM/h for F2. According to the Vmax and Km values of the ginsenosidase type III, the hydrolysis speed of these substrates by the enzyme was Rc>Rb1>Rb3>Rb2>Rg3(S)>Rd>F2 in order.

Signal transmission in a human body medium-based body sensor network using a Mach-Zehnder electro-optical sensor.

The signal transmission technology based on the human body medium offers significant advantages in Body Sensor Networks (BSNs) used for healthcare and the other related fields. In previous works we have proposed a novel signal transmission method based on the human body medium using a Mach-Zehnder electro-optical (EO) sensor. In this paper, we present a signal transmission system based on the proposed method, which consists of a transmitter, a Mach-Zehnder EO sensor and a corresponding receiving circuit. Meanwhile, in order to verify the frequency response properties and determine the suitable parameters of the developed system, in-vivo measurements have been implemented under conditions of different carrier frequencies, baseband frequencies and signal transmission paths. Results indicate that the proposed system will help to achieve reliable and high speed signal transmission of BSN based on the human body medium.

Box-Behnken optimization design and enhanced oral bioavailability of thymopentin-loaded poly (butyl cyanoacrylate) nanoparticles.

This study was done to prepare thymopentin (TP5)-loaded poly (butyl cyanoacrylate) nanoparticles (TP5-PBCA-NPs) and evaluate thier efficacy for oral delivery. TP5-PBCA-NPs were prepared by emulsion polymerization, and the formulation was optimized based on Box-Behnken experimental design. The physico-chemical characteristics of TP5-PBCA-NPs were evaluated using transmission electron microscopy (TEM), malvern zetasizer, Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The encapsulation efficiency, enzymatic degradation and release behavior of TP5-PBCA-NPs in various media were evaluated using a high-performance liquid chromatography (HPLC) method. The pharmacodynamic studies on oral administration of TP5-PBCA-NPs were performed in FACScan flow cytometry. An optimum formulation consisted of 0.7% poloxamer 188 (Pol), 0.6% dextran-70 (Dex), 0.1% sodium metabisulfite (Sm), 0.1% TP5 and 1% (v/v) n-butyl cyanoacrylate. The particle size and zeta potential of optimized TP5-PBCA-NPs was 212 nm and -22.6 mV respectively with 82.45% encapsulation efficiency. TP5 was entrapped inside the nanoparticles in molecular dispersion form. The release of TP5 from PBCA-NPs was pH dependent; the cumulative release percentage in 0.1 M HCI for 4 hours was less than 16% while it was more than 80% in pH6.8 PBS. The PBCA-NPs could efficiently protect TP5 from enzymatic degradation; the remained percentage of TP5 encapsulated in PBCA-NPs was 58.40% after incubated with trypsin in pH6.8 PBS for 4 h while it was only 32.29% for free drug. In the oral administration study in vivo, the lowered T-lymphocyte subsets values were significantly increased and the raised CD4+/CD8+ ratio was evidently reduced compared with that of TP5 solution (p < 0.05), and the improvement of bioavailability was dose-dependent. These results indicated that the PBCA nanoparticles may be a promising carrier for oral delivery of TP5.

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution.

Ophthalmic drug delivery with long pre-corneal retention time and high penetration into aqueous humor and intraocular tissues is the key-limiting factor for the treatment of ocular diseases and disorders. Within this study, the conjugate of cysteine-polyethylene glycol monostearate (Cys-PEG-SA) was synthesized and was used to compose the thiolated nanostructured lipid carrier (Cys-NLC) as a potential nanocarrier for the topical ocular administration of cyclosporine A (CyA). The rapid cross-linking process of Cys-PEG-SA in vitro was found in simulated physiological environment. The in vitro CyA release from Cys-NLC was slower than that of non-thiolated nanostructured lipid carriers (NLC) due to the cross-linking of thiomers on the surface of nanocarriers. After topical ocular administration in rabbits, the in vivo ocular distribution of CyA was investigated in comparison of Cys-NLC with non-thiolated NLCs and oil solution. The results showed that CyA concentration in systemic blood was very low and close to the detection limit. The area-under-the-curve (AUC(0-24h)) and mean retention time (MRT(0-24h)) of Cys-NLC group in aqueous humor, tear and eye tissues were significantly higher than that of oil solution, non-thiolated NLCs (p<0.05). These results demonstrated that the thiolated NLC could deliver high level of CyA into intraocular tissues due to its bioadhesive property and sustained release characteristics.

A novel lipoprotein-mimic nanocarrier composed of the modified protein and lipid for tumor cell targeting delivery.

Ursodeoxycholic acid (UA) modified protein-lipid nanocomplex (uP-LNC) as a novel biomimetic nanocarrier was developed for tumor-targeting delivery. Bovine serum albumin (BSA) was used as a model protein and its amino groups were covalently modified by UA. Lipid nanoparticle (LNP) composed of phospholipids, triglycerides and octadecylamine was prepared by using solvent evaporation method and was used as the core. UA modified BSA (uP) was attached onto the surface of LNP by post-insert method and generated the protein-lipid nanocomplex. As the control, cholesteryl hemiglutarate (CH), a non-targeting ligand was also used to modify BSA and then formed CH modified protein-lipid nanocomplex (cP-LNC). The combining efficiency of modified BSA with LNP, determined by Bradford protein assay, increased with the enhancement of substitution degree. The modified BSA and nanocomplex were characterized for the substitute degree, average molecular weight, surface tension, particle size and zeta potential by various physicochemical analyses. In vitro dissolution tests and cell uptake studies were performed by loading coumarin-6 as a fluorescent probe. The results indicated that the UA modified protein attached on the nanoparticles significantly decreased drug release from the nanocomplex in pH 7.4 medium, The uptake of uP-LNC was higher in hepatic carcinoma cells (HepG2 and Bel 7402) than in normal liver cells (L02). Furthermore, the uptake of uP-LNC was significantly higher than that of cP-LNC and LNP in these cells. The uptake was dependent on time, temperature and concentration, and could be inhibited by free UA. In addition, the MTT assay of uP-LNC and u(x)P with various degrees of substitution showed very low cytotoxicity at tested concentrations in all cells. The UA modification served to facilitate the specific receptor and energy mediated endocytosis process of the protein-lipid nanocomplex and enabled this nanocomplex to be a potential nanocarrier for tumor-targeting drug delivery.