[Levels of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in children with hand-foot-mouth disease].

OBJECTIVE: To study the clinical value of lymphocyte subsets, immunoglobulins, and complement C3 and C4 in the evaluation of immune status in children with hand-foot-mouth disease (HFMD). METHODS: A total of 282 children with HFMD were enrolled as the HFMD group, and 130 healthy children were enrolled as the healthy control group. The percentages of peripheral CD3+, CD4+, and CD8+ T lymphocytes, CD19+ B lymphocytes, and CD56+ natural killer cells were measured. The CD4+/CD8+ ratio was calculated. The levels of immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), and complement C3 and C4 were measured. RESULTS: The multivariate analysis showed that compared with the healthy control group, the HFMD group had significantly lower percentages of CD3+, CD4+, and CD8+ T lymphocytes and levels of complement C3 and C4 (P<0.05), as well as significantly higher percentage of CD56+ natural killer cells and level of IgG (P<0.05). The individual effect analysis showed that the children aged 0-3 years in the HFMD group had a significantly higher CD4+/CD8+ ratio than the healthy control group (P<0.05); boys aged 0-3 and ≥3 years in the HFMD group had a significantly higher level of IgM than the healthy control group (P<0.05); boys aged ≥3 years and girls aged 0-3 years in the HFMD group had a significantly lower level of IgA than the healthy control group (P<0.05). CONCLUSIONS: Cellular and humoral immunity disorders are observed in children with HFMD. The monitoring of lymphocyte subsets and immunoglobulin levels can provide a laboratory basis for immune status assessment in children with HFMD.

A sensitive and low background fluorescent sensing strategy based on g-C3N4-MnO2 sandwich nanocomposite and liposome amplification for ricin detection.

Ricin is an extremely potent ribosome-inactivating protein and serves as a likely food biocontaminant or biological weapon. Thus, simple, sensitive and accurate analytical assays capable of detecting ricin are urgently needed to be established. Herein, we present a novel method for ricin B-chain (RTB) detection by using two materials: (a) a highly efficient hybrid probe that was formed by linking a glucose oxidase (GOD)-encapsulated liposome (GOD-L) to magnetic beads (MBs) through hybridization between an aptamer and a blocker and (b) a new low-background g-C3N4-MnO2 sandwich nanocomposite that exhibits fluorescence resonance energy transfer (FRET) between the g-C3N4 nanosheet and MnO2. In the presence of RTB, the strong binding between RTB and the aptamer can release the blocker-linked liposome from the surface of the MBs. After magnetic separation, the decomposed liposome can release GOD to catalyze the oxidation of glucose, generating a certain amount of H2O2. Then, H2O2 can reduce MnO2 of the g-C3N4-MnO2 nanocomposite to Mn2+, which leads to the elimination of FRET. Thus, the fluorescence of the g-C3N4 nanosheet will be turned on. Because of the excellent signal amplification ability of liposome and the characteristic highly sensitive response of the g-C3N4-MnO2 nanocomposite toward H2O2, RTB could be detected sensitively based on the significantly enhanced fluorescent intensity. The linear range of detection was from 0.25 µg mL-1 to 50 µg mL-1 and the limit of detection (LOD) was 190 ng mL-1. Moreover, the proposed assay was successfully applied in the detection of the entire ricin toxin content in a castor seed.

Proteomic analysis of lettuce seed germination and thermoinhibition by sampling of individual seeds at germination and removal of storage proteins by polyethylene glycol fractionation.

Germination and thermoinhibition in lettuce (Lactuca sativa 'Jianyexianfeng No. 1') seeds were investigated by a proteomic comparison among dry seeds, germinated seeds at 15°C, at 15°C after imbibition at 25°C for 48 h, or at 25°C in KNO3 (all sampled individually at germination), and ungerminated seeds at 25°C, a thermoinhibitory temperature. Before two-dimensional gel electrophoresis analysis, storage proteins (greater than 50% of total extractable protein) were removed by polyethylene glycol precipitation, which significantly improved the detection of less abundant proteins on two-dimensional gels. A total of 108 protein spots were identified to change more than 2-fold (P<0.05) in abundance in at least one germination treatment. Nineteen proteins increasing and one protein decreasing in abundance during germination had higher abundance in germinated 15°C, 15°C after imbibition at 25°C for 48 h, and 25°C in KNO3 seeds than in ungerminated 25°C seeds. Gene expression of 12 of those proteins correlated well with the protein accumulation. Methionine metabolism, ethylene production, lipid mobilization, cell elongation, and detoxification of aldehydes were revealed to be potentially related to lettuce seed germination and thermoinhibition. Accumulation of three proteins and expression of five genes participating in the mevalonate (MVA) pathway of isoprenoid biosynthesis correlated positively with seed germinability. Inhibition of this pathway by lovastatin delayed seed germination and increased the sensitivity of germination to abscisic acid. MVA pathway-derived products, cytokinins, partially reversed the lovastatin inhibition of germination and released seed thermoinhibition at 25°C. We conclude that the MVA pathway for isoprenoid biosynthesis is involved in lettuce seed germination and thermoinhibition.

Characterization of a marine-derived dextranase and its application to the prevention of dental caries.

The dextranase added in current commercial dextranase-containing mouthwashes is largely from fungi. However, fungal dextranase has shown much higher optimum temperature than bacterial dextranase and relatively low activity when used in human oral cavities. Bacterial dextranase has been considered to be more effective and suitable for dental caries prevention. In this study, a dextranase (Dex410) from marine Arthrobacter sp. was purified and characterized. Dex410 is a 64-kDa endoglycosidase. The specific activity of Dex410 was 11.9 U/mg at optimum pH 5.5 and 45 °C. The main end-product of Dex410 was isomaltotriose, isomaltoteraose, and isomaltopentaose by hydrolyzing dextran T2000. In vitro studies showed that Dex410 effectively inhibited the Streptococcus mutans biofilm growth in coverage, biomass, and water-soluble glucan (WSG) by more than 80, 90, and 95 %, respectively. The animal experiment revealed that for short-term use (1.5 months), both Dex410 and the commercial mouthwash Biotene (Laclede Professional Products, Gardena, CA, USA) had a significant inhibitory effect on caries (p = 0.0008 and 0.0001, respectively), while for long-term use (3 months), only Dex410 showed significant inhibitory effect on dental caries (p = 0.005). The dextranase Dex410 from a marine-derived Arthrobacter sp. strain possessed the enzyme properties suitable to human oral environment and applicable to oral hygiene products.

Enzyme-Mineralized PVASA Hydrogels with Combined Toughness and Strength for Bone Tissue Engineering.

Enzymatic mineralization is an advanced mineralization method that is often used to enhance the stiffness and strength of hydrogels, but often accompanied by brittle behavior. Moreover, the hydrogel systems with dense networks currently used for enzymatic mineralization are not ideal materials for bone repair applications. To address these issues, two usual bone repair hydrogels, poly(vinyl alcohol) (PVA) and sodium alginate (SA), were selected to form a double-network structure through repeated freeze-thawing and ionic cross-linking, followed by enzyme mineralization. The results demonstrated that both enzymatic mineralization and double-network structure improved the mechanical and biological properties and even exhibited synergistic effects. The mineralized PVASA hydrogels exhibited superior comprehensive mechanical properties, with a Young's modulus of 1.03 MPa, a storage modulus of 103 kPa, and an equilibrium swelling ratio of 132%. In particular, the PVASA hydrogel did not suffer toughness loss after mineralization, with a high toughness value of 1.86 MJ/m3. The prepared hydrogels also exhibited superior biocompatibility with a cell spreading area about 13 times that of mineralized PVA. It also effectively promoted cellular osteogenic differentiation in vitro and further promoted the formation of new bone in the femur defect region in vivo. Overall, the enzyme-mineralized PVASA hydrogel demonstrated combined strength and toughness and great potential for bone tissue engineering applications.

Galactose-functionalized cationic polycarbonate diblock copolymer for targeted gene delivery to hepatocytes.

To mediate selective gene delivery to hepatocytes via the asialoglycoprotein receptors (ASGP-Rs), we designed and synthesized well-defined and narrowly dispersed galactose- and glucose-functionalized cationic polycarbonate diblock copolymers (designated as Gal-APC and Glu-APC, respectively) using organocatalytic ring-opening polymerization of functionalized carbonate monomers, with a subsequent quaternization step using bis-tertiary amines to confer quaternary and tertiary amines for DNA binding and endosomal buffering, respectively. The sugar-functionalized diblock copolymers effectively bound and condensed DNA to form positively charged nanoparticles (<100 nm in diameter and ≈30 mV zeta-potential) that were stable under high physiological salt conditions. In comparison to the control Glu-APC/DNA complexes, Gal-APC/DNA complexes mediated significantly higher gene expression in ASGP-R positive HepG2 cells with no significant difference observed in ASGP-R negative HeLa cells. The co-incubation of Gal-APC/DNA complexes with a natural ASGP-R ligand effectively led to a decrease in gene expression, hence providing evidence for the ASGP-R mediated endocytosis of the polyplexes. Importantly, the Gal-APC/DNA complexes induced minimal cytotoxicities in HepG2 cells at the N/P ratios tested. Taken together, the galactose-functionalized cationic polycarbonate diblock copolymer has potential for use as a non-viral gene vector for the targeted delivery of therapeutic genes to hepatocytes in the treatment of liver diseases.

Evaluation of fixation of expandable implants in the mandibles of ovariectomized sheep.

PURPOSE: This study aimed to investigate the effects of an expandable implant (EI) in ovariectomized sheep. METHODS: The EI and taper implant (control group) were produced and placed in mandibles of ovariectomized sheep. Twelve weeks after implantation, resonance frequency analysis, biomechanical tests, histomorphometry, and micro-computed tomography were applied to detect the osseointegration in the 2 groups. RESULTS: The implant stability quotient values, maximal pullout forces, and bone-implant contact (BIC) were 60.3 ± 7.9, 511.0 ± 18.7 N, and 53.14% ± 4.56%, respectively, in the EI group and 58.3 ± 8.9, 394.5 ± 54.5 N, and 46.85% ± 5.04%, respectively, in the control group. There was no significant difference between the 2 groups in implant stability quotient values (P > .05); however, in the EI group the maximal pullout force and BIC were increased significantly (P < .05 and P < .01, respectively). Micro-computed tomography analysis showed that the bone volume/total volume ratio and trabecular number increased significantly (P < .01) and trabecular separation decreased significantly (P < .05) in the EI group. CONCLUSIONS: EI could improve osseointegration in osteoporosis after 12 weeks of implantation by increasing BIC around the implant and by supplying an extra osseointegration surface.

[Analysis of clinical features and early warning indicators of death from hand, foot and mouth disease in Shandong province].

OBJECTIVE: To understand the clinical features of death from hand, foot and mouth disease (HFMD) and to explore the early warning index of HFMD death. METHODS: A total of 41 HFMD death cases were collected as case group in Shandong province between 2009 and 2011, and another 123 serious HFMD cases were selected as control group according to the similar gender, place of origin and hospital level, with the ratio at 1:3. We investigated the general situation, clinical treatment, past medical history, clinical symptoms and signs of the ill children, and applied the conditional logistic regression to explore early warning index of HFMD death. RESULTS: The rate of patients who had symptoms in nervous system, digestive system, circulatory system and respiratory system were separately 90.2% (37/41), 58.5% (24/41), 53.7% (22/41) and 90.2% (37/41) in case group; and the proportions were 44.7% (55/123), 13.8% (17/123), 10.6% (13/123) and 12.2% (15/123) respectively in control group. The difference between the two groups showed statistical significance (χ(2) = 25.881, 32.791, 34.011, 86.505, P < 0.05). In case group, 37 patients had neurogenic pulmonary edema, 26 patients got encephalitis, 15 patients had respiratory and circulatory failure, 7 patients got pulmonary hemorrhage, 4 patients had multiple organ failure, 4 patients got myocarditis and 1 patient had cerebral hernia. According to multi-factor logistic regression analysis, the early warning indicators of HFMD death included neck resistance (case group: 34.1% (14/41), control group: 4.1% (5/123); OR = 7.145, 95%CI: 1.748 - 29.204), vomiting (case group: 58.5% (24/41), control group: 13.8% (17/123); OR = 5.632, 95%CI: 1.793 - 17.685) and increase of heart rate (case group: 53.7% (22/41), control group: 10.6% (14/123), OR = 6.370, 95%CI: 1.517 - 26.743). CONCLUSION: In the process of clinical treatment and care, we should interfere the serious HFMD patients with neck resistance, vomiting and increase of heart rate, and thereby reduce the death from HFMD.

Electrostatic assemblies of molecularly imprinted polymers on the surface of electrospun nanofiber membranes for the point-of-care detection of thiodiglycol, a sulfur mustard poisoning metabolic marker.

In this study, molecularly imprinted polymers (MIPs) were assembled on the surface of ethylene imine polymer (PEI)/poly(vinyl alcohol) (PVA) electrospun nanofiber membranes for the point-of-care testing (POCT) of thiodiglycol (TDG), a sulfur mustard poisoning metabolic marker, using concentrated gold nanoparticles (AuNPs) as the signal reporting units. The MIPs/PEI/PVA nanofiber membranes could capture TDG specifically through the recognition interaction between MIPs and TDG. Then, AuNPs were adsorbed onto the MIPs/PEI/PVA nanofiber membranes through the Au-S interaction between TDG and AuNPs to produce a visible red color. In order to improve the sensitivity, the silver-enhanced solutions were used to deepen the color of the nanofiber membranes and the software Image J was used to read the gray value as the signal response for subsequent analysis. There was a good linear relationship between the color change of the MIPs/PEI/PVA nanofiber membranes and the TDG concentration from 0.1 ng mL-1 to 1.0 µg mL-1, and the limit of detection was 38 pg mL-1. This method was applied for the selective detection of TDG in urine, showing great potential for the clinical diagnosis of mustard gas poisoning.

Co-detection in the pathogenesis of severe hand-foot-mouth disease.

It still needs to be elucidated whether co-detection of EV71 with other intestinal tract viruses plays a role in the pathogenesis of severe hand-foot-mouth disease (HFMD). A total of 680 stool specimens collected from clinically diagnosed mild and severe-HFMD patients were tested for EV71, CA16, norovirus, bocavirus and rotavirus. The results showed that EV71 was significantly associated with severe-HFMD patients. Co-detection of EV71 with norovirus and rotavirus was also significantly associated with severe-HFMD patients: The OR (95 % CI) value was 6.466 (2.735, 15.283) and 7.561 (3.560, 16.057), p < 0.001, respectively. Co-detection of EV71 with rotavirus or norovirus is probably associated with severe HFMD.

Construction of novel antiplatelet modified polyethersulfone membrane and study into its blood compatibility.

Blood purification therapy is widely used in patients with renal insufficiency and severe infections, where membrane-associated thrombosis is a side effect. How to improve the hemocompatibility of dialysis membranes and reduce thrombosis is a focus of current research, in which platelets play a key role. However, few dialysis membranes that directly inhibit platelets have been developed to date. In this study, a polyethersulfone (PES) membrane was modified with ticagrelor, a platelet P2Y12 receptor inhibitor, and detailed characterization was performed. The ticagrelor modified PES membrane (TMPES) showed good hydrophilicity and anti-protein adsorption and significantly inhibited platelet adhesion, aggregation, and activation, which demonstrated good antithrombotic properties. In addition, the membrane had excellent red blood cell (RBC) compatibility, anticoagulant, and antiinflammatory effects, which demonstrated superior biosafety in cell and animal experiments. Therefore, the TMPES dialysis membrane could have potential in clinical applications.

Corrigendum to "Scaffolds of bioactive glass (Bioglass®) combined with recombinant human bone morphogenetic protein -9 (rhBMP-9) for tooth extraction site preservation" [Heliyon 8 (1) (January 2022) e08796].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e08796.].

In situ regulation of bacterial cellulose networks by starch from different sources or amylose/amylopectin content during fermentation.

Bacterial cellulose (BC) is a promising biopolymer, but its three-dimensional structure needs to be controllable to be used in multiple fields. BC has some advantages over other types of cellulose, not only in terms of purity and properties but also in terms of modification (in situ modification) during the synthesis process. Here, starches from different sources or with amylose/amylopectin content were added to the growth medium to regulate the structural properties of BC in-situ. The obtained BC membranes were further modified by superhydrophobic treatment for oil-water separation. Starches alter the viscosity of the medium, thus affecting bacterial motility and cellulose synthesis, and adhere to the microfibers, limiting their further polymerization and ultimately altering the membrane porosity, pore size, and mechanical properties perpendicular to the BC fibril layer direction. The average pore diameter of the BC/PS membrane increased by 1.94 times compared to the initial BC membrane. The chemically modified BC/PS membrane exhibited super-hydrophobicity (water contact angle 167°), high oil-water separation flux (dichloromethane, 23,205 Lm-2 h-1 MPa-1), high separation efficiency (>97%). The study provides a foundation for developing methods to regulate the network structure of BC and broaden its application.

Catalytic hairpin assembly mediated liposome-encoded magnetic beads for signal amplification of peroxide test strip based point-of-care testing of ricin.

Herein, we propose a new peroxide test strip (PTS) based point-of-care testing (POCT) method to detect ricin B-chain qualitatively and quantitatively by using catalytic hairpin assembly (CHA) mediated liposome-encoded magnetic beads for signal amplification. The sensitivity of this PTS based POCT method was improved significantly because it combined CHA signal amplification and liposome-based signal amplification.

Fabrication of dually N/S-doped carbon from biomass lignin: Porous architecture and high-rate performance as supercapacitor.

The lignin amine (LA) was exploited to prepare dually N/S-doped carbon (NSC), which was endowed with intriguing porous structure by Fe3O4 template. N and S elements, originating from LA, are doped into the materials. NSC possesses diverse-scale 3D pores. The macropores are made by Fe3O4, which facilitate to produce meso and micro pores on their walls by KOH activation. The sample prepared at 700 °C (NSC-700) is found to have the largest specific surface area (1199 cm2 g-1) and specific capacity (241 F g-1 at current density of 1 A g-1). Its capacity is 260% as high as that of lignin amine carbon (LAC) prepared without adding Fe3O4. Excellent rate performance is unraveled because of possessing 82% specific capacity at 20 A g-1 and 27.2 Wh kg-1 energy density at 10000 W kg-1 power density. Moreover, the specific capacity maintains 95.0% after 3000 cycles, indicating good electrochemical stability. The good electrical performance of NSC-700 is attributed to its interesting electronic properties that are induced by special pore structure. Because of having merits such as high rate performance, long life, large specific capacity and low cost, our NSC is anticipated to be a promising capacitor as electrode material.

Construction of heterostructured g-C3N4/ZnO/cellulose and its antibacterial activity: experimental and theoretical investigations.

A g-C3N4/ZnO/cellulose ternary composite (labeled as CNZCel) with an ordered structure and excellent antibacterial properties has been successfully synthesized via a facile method. Its morphology, microstructure and components have been analyzed by using XRD, SEM, TEM and EDS, and the results corroborate the co-existence of three components in the ternary composite. It is revealed that ZnO particles are connected to the layered g-C3N4 and simultaneously attached to the cellulose substrate. This microstructural feature is also borne out by the relativistic density functional study of a finite g-C3N4-ZnO-cellulose cluster. Both experimental and theoretical results unravel that the interfacial bonding interactions in the ternary composite improve electron transfer among components and enable high-efficiency spatial separation of photogenerated electrons and holes. Consequently, good antibacterial performance of the composite has been found in tests. This study provides the prospect of preparing low-cost and environment-friendly food packaging materials, which are also endowed with excellent antibacterial activity.

[In vitro study of antimicrobial efficacy of different irrigations on Enterococcus faecalis biofilm formation in root canal].

PURPOSE: To compare the antimicrobial effect of different irrigations on Enterococcus faecalis biofilms in extracted teeth and evaluate the antimicrobial activity of irrigating solutions residual against E. faecalis biofilms formation, in order to provide a better strategy for clinician. METHODS: Extracted human premolar teeth with single root canal were clearly autoclaved. These teeth were contaminated with E. faecalis（ATCC33186） and incubated for 60 days. The samples were randomly assigned to 4 experimental groups. During biomechanical instrumentation, the root canal was irrigated with different irrigating agents. The bacteria samples were collected with sterile paper points before and after instrumentation to F2. Then, samples that had been instrumented and autoclaved again were randomly divided into 2 groups treated with normal saline and 1%NaOCl for 30 min. E. faecalis was used to contaminate these root canals. The bacteria samples were collected with sterile paper points after 2, 6, 24, 48 h. SPSS19.0 software package was used for statistical analysis. RESULTS: Group using 1% NaOCI with ultrasound devices was significantly more effective than NS alone groups. 1% NaOCI groups showed a better residual activity than NS group. CONCLUSIONS: NaOCl is still the most important irrigating solutions, and it could be a better choice after biomechanical instrumentation, because of its long time substantivity achieves residual antimicrobial activity. Ultrasound devices is recommended to coordinate with irrigation.

Carrier-Enhanced Anticancer Efficacy of Sunitinib-Loaded Green Tea-Based Micellar Nanocomplex beyond Tumor-Targeted Delivery.

Although a few nanomedicines have been approved for clinical use in cancer treatment, that recognizes improved patient safety through targeted delivery, their improved efficacy over conventional drugs has remained marginal. One of the typical drawbacks of nanocarriers for cancer therapy is a low drug-loading capacity that leads to insufficient efficacy and requires an increase in dosage and/or frequency of administration, which in turn increases carrier toxicity. In contrast, elevating drug-loading would cause the risk of nanocarrier instability, resulting in low efficacy and off-target toxicity. This intractable drug-to-carrier ratio has imposed constraints on the design and development of nanocarriers. However, if the nanocarrier has intrinsic therapeutic effects, the efficacy would be synergistically augmented with less concern for the drug-to-carrier ratio. Sunitinib-loaded micellar nanocomplex (SU-MNC) was formed using poly(ethylene glycol)-conjugated epigallocatechin-3-O-gallate (PEG-EGCG) as such a carrier. SU-MNC specifically inhibited the vascular endothelial growth factor-induced proliferation of endothelial cells, exhibiting minimal cytotoxicity to normal renal cells. SU-MNC showed enhanced anticancer effects and less toxicity than SU administered orally/intravenously on human renal cell carcinoma-xenografted mice, demonstrating more efficient effects on anti-angiogenesis, apoptosis induction, and proliferation inhibition against tumors. In comparison, a conventional nanocarrier, SU-loaded polymeric micelle (SU-PM) comprised of PEG-b-poly(lactic acid) (PEG-PLA) copolymer, only reduced toxicity with no elevated efficacy, despite comparable drug-loading and tumor-targeting efficiency to SU-MNC. Improved efficacy of SU-MNC was ascribed to the carrier-drug synergies with the high-performance carrier of PEG-EGCG besides tumor-targeted delivery.

Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China.

Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains (n = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the VP1 gene from a larger CVA4 collection (n = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, VP1 was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of VP1 was estimated to be 5.12 × 10-3 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in VP1 gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China.

Highly Augmented Drug Loading and Stability of Micellar Nanocomplexes Composed of Doxorubicin and Poly(ethylene glycol)-Green Tea Catechin Conjugate for Cancer Therapy.

Low drug loading and instability in blood circulation are two key challenges that impede the successful clinical translation of nanomedicine, as they result in only marginal therapeutic efficacy and toxic side effects associated with premature drug leakage, respectively. Herein, highly stable and ultrahigh drug loading micellar nanocomplexes (MNCs) based on the self-assembly of the anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3-O-gallate (EGCG) conjugate are developed. The formation of these MNCs is facilitated by strong favorable intermolecular interactions between the structurally similar aromatic EGCG and DOX molecules, which impart exceptionally high drug-loading capability of up to 88% and excellent thermodynamic and kinetic stability. Unlike two clinical formulations of DOX-free DOX and liposomal DOX, which are not effective below their lethal dosages, these DOX-loaded MNCs demonstrate significant tumor growth inhibition in vivo on a human liver cancer xenograft mouse model with minimal unwanted toxicity. Overall, these MNCs can represent a safe and effective strategy to deliver DOX for cancer therapy.