Shape and Shear Stress Impact on the Toxicity of Mesoporous Silica Nanoparticles: In Vitro and In Vivo Evidence.

Mesoporous silica nanoparticles (MSNs) are widely used in the biomedical field because of their unique and excellent properties. However, the potential toxicity of different shaped MSNs via injection has not been fully studied. This study aims to systematically explore the impact of shape and shear stress on the toxicity of MSNs after injection. An in vitro blood flow model was developed to investigate the cytotoxicity and the underlying mechanisms of spherical MSNs (S-MSN) and rodlike MSNs (R-MSN) in human umbilical vein endothelial cells (HUVECs). The results suggested that the interactions between MSNs and HUVECs under the physiological flow conditions were significantly different from that under static conditions. Whether under static or flow conditions, R-MSN showed better cellular uptake and less oxidative damage than S-MSN. The main mechanism of cytotoxicity induced by R-MSN was due to shear stress-dependent mechanical damage of the cell membrane, while the toxicity of S-MSN was attributed to mechanical damage and oxidative damage. The addition of fetal bovine serum (FBS) alleviated the toxicity of S-MSN by reducing cellular uptake and oxidative stress under static and flow conditions. Moreover, the in vivo results showed that both S-MSN and R-MSN caused cardiovascular toxicity in zebrafish and mouse models due to the high shear stress, especially in the heart. S-MSN led to severe oxidative damage at the accumulation site, such as liver, spleen, and lung in mice, while R-MSN did not cause significant oxidative stress. The results of in vitro blood flow and in vivo models indicated that particle shape and shear stress are crucial to the biosafety of MSNs, providing new evidence for the toxicity mechanisms of the injected MSNs.

Apoptosis-Sensing Xenograft Zebrafish Tumor Model for Anticancer Evaluation of Redox-Responsive Cross-Linked Pluronic Micelles.

A suitable animal model for preclinical screening and evaluation in vivo could vastly increase the efficiency and success rate of nanomedicine development. Compared with rodents, the transparency of the zebrafish model offers unique advantages of real-time and high-resolution imaging of the whole body and cellular levels in vivo. In this research, we established an apoptosis-sensing xenograft zebrafish tumor model to evaluate the anti-cancer effects of redox-responsive cross-linked Pluronic polymeric micelles (CPPMs) visually and accurately. First, doxorubicin (Dox)-loaded CPPMs were fabricated and characterized with glutathione (GSH)-responsive drug release. Then, the B16F10 xenograft zebrafish tumor model was established to mimic the tumor microenvironment with angiogenesis and high GSH generation for redox-responsive tumor-targeting evaluation in vivo. The high GSH generation was first verified in the xenograft zebrafish tumor model. Compared with ordinary Pluronic polymeric micelles, Dox CPPMs had a much higher accumulation in zebrafish tumor sites. Finally, the apoptosis-sensing B16F10-C3 xenograft zebrafish tumor model was established for visual, rapid, effective, and noninvasive assessment of anti-cancer effects at the cellular level in vivo. The Dox CPPMs significantly inhibited the proliferation of cancer cells and induced apoptosis in the B16F10-C3 xenograft zebrafish tumor model. Therefore, the redox-responsive cross-linked Pluronic micelles showed effective anti-cancer therapy in the xenograft zebrafish tumor model. This xenograft zebrafish tumor model is available for rapid screening and assessment of anti-cancer effects in preclinical studies.

Highly Foldable, Super-Sensitive, and Transparent Nanocellulose/Ceramic/Polymer Cover Windows for Flexible OLED Displays.

Polymer cover windows are important components of flexible OLED displays but they easily generate wrinkles because of their weak folding resistance. Increasing the polymer thickness can improve the folding resistance but it decreases the touch sensitivity. Thus, fabricating highly foldable and supersensitive polymer cover windows is still challenging. Here, by incorporating cellulose nanocrystals (CNCs) and zirconia (ZrO2) into colorless polyimide (CPI), we developed a highly foldable and supersensitive hybrid cover window. Inspired by the theory of elasticity, we added rigid CNCs into CPI to improve the elastic modulus and hence the foldability. ZrO2 was introduced to improve dielectric properties, which leads to improved touch sensitivity. After these modifications, the elastic modulus of the cover windows was increased from 1432 to 2221 MPa, whereas its dielectric constant was increased from 2.95 to 3.46 (@1 × 106 Hz), resulting in significantly enhanced foldability and sensitivity. Meanwhile, because of the nano size of CNCs and ZrO2, the hybrid cover windows exhibit excellent optical properties with the transmittance of ∼88.1%@550 nm and haze of 2.39%. With improved and balanced mechanical, dielectric, and optical properties, these hybrid cover windows overcome current cover windows' defects and could be widely used in next-generation flexible displays.

Highly Soluble and Stable, High Release Rate Nanocellulose Codrug Delivery System of Curcumin and AuNPs for Dual Chemo-Photothermal Therapy.

As a natural antitumor drug, curcumin (CUR) has received increasing attention from researchers and patients due to its various medicinal properties. However, currently CUR is still restricted due to its low and stand-alone therapeutic effects that seriously limit its clinical application. Here, by using cellulose nanocrystals (CNCs) as a nanocarrier to load CUR and AuNPs simultaneously, we developed a hybrid nanoparticle as a codrug delivery system to enhance the low and stand-alone therapeutic effects of CUR. Aided with the encapsulation of ß-cyclodextrin (ßCD), both the solubility and the stability of CUR are greatly enhanced (solubility increased from 0.89 to 131.7 µg/mL). Owing to the unique rod-like morphology of CNCs, the system exhibits an outstanding loading capacity of 31.4 µg/mg. Under the heat effects of coloaded AuNPs, the system demonstrates a high release rate of 77.63%. Finally, with CNC as a bridge nanocarrier, all aforementioned functions were integrated into one hybrid nanoparticle. The all-in-one integration ensures CUR to have enhanced therapeutic effects and enables the delivery system to exhibit combined chemo-photothermal therapy outcomes. This work presents a significant step toward CUR's clinical application and provides a new strategy for effective and integrative treatment of tumor disease.

Particle Integrity and Size Effect on the Journey of Polymeric Nanocarriers in Zebrafish Model and the Correlation with Mice.

Polymeric nanocarriers have high biocompatibility for potential drug delivery applications. After entering bloodstream, nanocarriers will circulate, interact with proteins, dissociate, or be cleared by reticuloendothelial system. Zebrafish as a visual animal model, can serve as a tool for screening nanomedicines and monitoring nanocarrier behaviors in vivo. However, a comprehensive correlation between zebrafish and rodent models is currently deficient. Here, different-sized poly(caprolactone) nanocarriers (PCL NCs) are fabricated with or without PEGylation to investigate correlation between zebrafish and mice regarding their biofate via Förster resonance energy transfer technique. Results show that PEGylated PCL NCs have higher integrity in both zebrafish and mice. Small PEG-PCL NCs have longer circulation, while large PEG-PCL NCs have dramatically higher macrophage sequestration in zebrafish and mice spleen, leading to poor circulation. PCL NCs dissociate rapidly with less macrophage sequestration. Moreover, in 7 days postfertilization (dpf) zebrafish, polymers are eliminated via hepatobiliary pathway, which is not fully functional at earlier stages of development. The effects of nanocarrier integrity on macrophage sequestration in zebrafish and good correlation with mice spleen are pioneered to be demonstrated. The findings suggest that 7 dpf zebrafish are suitable as an in vivo screening model of nanocarriers and predict their biofate in rodents.

Flexible, transparent and tough silver nanowire/nanocellulose electrodes for flexible touch screen panels.

Flexible touch screen panel (f-TSP) has been emerging recently and metallic nanowire transparent conductive electrodes (TCEs) are its key components. However, most metallic nanowire (MNW) TCEs suffer from weak bonding strength between metal nanowire electrode layers and polymer substrates, which causes delamination of TCEs and produces serious declines in durability of f-TSPs. Here, we introduce AgS bonding and develop tough and strong electrode-substrate bonded MNW TCEs, which can enhance durability of f-TSPs significantly. We used silver nanowires (AgNWs) as metal conductive electrode and thiol-modified nanofibrillated cellulose (NFC-HS) nanopaper as substrates. Because of the existence of Ag from AgNWs and S from NFC-HS, strong AgS bonding was generated and tough TCEs were obtained. The TCEs exhibit excellent electrical stability, outstanding optical and electrical properties. The f-TSP devices integrated with the TCEs illustrate striking durability. This technique may provide a promising strategy to produce flexible and tough TCEs for next-generation high-durability f-TSPs.

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model.

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) could treat Imiquimod (IMQ)-induced psoriasis-like mice. The objective of this study is to further elucidate biofate of PLGA NPs after intradermal delivery including DCs uptake, and their further trafficking in psoriasis-like mice model by using fluorescence probes. Two-sized DiO/DiI-loaded PLGA NPs of 50 ± 4.9 nm (S-NPs) and 226 ± 7.8 nm (L-NPs) were fabricated, respectively. In vitro cellular uptake results showed that NPs could be internalized into DCs with intact form, and DCs preferred to uptake larger NPs. Consistently, in vivo study showed that L-NPs were more captured by DCs and NPs were firstly transported to skin-draining lymph nodes (SDLN), then to spleens after 8 h injection, whereas more S-NPs were transported into SDLN and spleens. Moreover, FRET imaging showed more structurally intact L-NPs distributed in skins and lymph nodes. In conclusion, particle size can affect the uptake and trafficking of NPs by DCs in skin and lymphoid system, which needs to be considered in NPs tailing to treat inflammatory skin disease like psoriasis.

Disintegrable, transparent and mechanically robust high-performance antimony tin oxide/nanocellulose/polyvinyl alcohol thermal insulation films.

Polymer-based thermal insulation films are widely utilized to reduce the influence of solar radiation. However, current thermal insulation films face several challenges from poor thermal insulation performance and severe environmental pollution, which are caused by the non-disintegratability of polymer substrates. Here, cellulose nanofiber (CNF)/antimony tin oxide (ATO) hybrid films with and without polyvinyl alcohol (PVA) are presented and they can be used as window thermal barrier films and personal thermal management textiles. The hybrid films exhibit prominent thermal insulation performance, blocking 91.07% ultraviolet(UV) light, reflecting 95.19% near-infrared(NIR) light, and transmitting 44.89% visible(VIS) light. Meanwhile, the hybrid films demonstrate high thermal stability, high anti-UV aging stability, and robust mechanical properties. Moreover, the used-up hybrid films based on natural cellulose are of high disintegratability and recyclability. Our present work is anticipated to open up a new avenue for the fabrication of next-generation high-performance thermal insulation films with sustainable and environmentally friendly processes.

Correlations and Prognostic Roles of the Nutritional Status and Neutrophil-to-lymphocyte Ratio in Elderly Patients with Acute Myocardial Infarction Undergoing Primary Coronary Intervention.

The prognostic capacities of nutritional status and inflammation in patients with acute myocardial infarction (AMI) have attracted increasing interest. However, the combined usefulness of the Controlling Nutritional Status (CONUT) score and neutrophil-to-lymphocyte ratio (NLR) in predicting adverse outcomes has not been investigated. The aim of our study was to investigate the relationship between the CONUT score and the NLR in patients with AMI and assessing the potential of these factors as prognostic markers.In this retrospective study, we reviewed the medical records of consecutive patients aged 65 years or older who were diagnosed with AMI and who underwent primary coronary intervention. We assessed the nutritional and inflammatory statuses using the CONUT score and the NLR, respectively. The NLR and CONUT score in the major adverse cardiovascular event (MACE) (+) patients were significantly higher than those in the MACE (-) patients. The areas under the receiver operating characteristic curves of the NLR and CONUT score were 0.71 and 0.77, respectively. The Kaplan-Meier analysis showed that patients with a high NLR (≥6.07) and CONUT score (≥3.5) had the worst prognoses. The multivariate Cox proportional hazards analyses suggested that the CONUT score was an independent predictor.The CONUT score was proven to be a significant prognostic factor of clinical outcomes in patients with AMI. However, further research in this area is needed to more fully understand the relationship among nutritional status, inflammation, and cardiovascular diseases, which might help reduce MACEs in patients with AMI.

Highly Thermally Stable, Green Solvent Disintegrable, and Recyclable Polymer Substrates for Flexible Electronics.

Flexible electronics require its substrate to have adequate thermal stability, but current thermally stable polymer substrates are difficult to be disintegrated and recycled; hence, generate enormous electronic solid waste. Here, a thermally stable and green solvent-disintegrable polymer substrate is developed for flexible electronics to promote their recyclability and reduce solid waste generation. Thanks to the proper design of rigid backbones and rational adjustments of polar and bulky side groups, the polymer substrate exhibits excellent thermal and mechanical properties with thermal decomposition temperature (Td,5% ) of 430 °C, upper operating temperature of over 300 °C, coefficient of thermal expansion of 48 ppm K-1 , tensile strength of 103 MPa, and elastic modulus of 2.49 GPa. Furthermore, the substrate illustrates outstanding optical and dielectric properties with high transmittance of 91% and a low dielectric constant of 2.30. Additionally, it demonstrates remarkable chemical and flame resistance. A proof-of-concept flexible printed circuit device is fabricated with this substrate, which demonstrates outstanding mechanical-electrical stability. Most importantly, the substrate can be quickly disintegrated and recycled with alcohol. With outstanding thermally stable properties, accompanied by excellent recyclability, the substrate is particularly attractive for a wide range of electronics to reduce solid waste generation, and head toward flexible and "green" electronics.

Toward understanding the prolonged circulation and elimination mechanism of crosslinked polymeric micelles in zebrafish model.

Understanding the behaviors of nanomedicines in vivo is one of the most important prerequisites for the design and optimization of nanomedicines. However, the in vivo tracking of nanomedicines in rodents is severely limited by the restricted imaging possibilities within these animals. To meet these needs, the FRET (fluorescence or Förster resonance energy transfer) imaging combined with visual zebrafish larvae model (7 dpf) was used to study the behaviors of polymeric micelles in vivo at high spatiotemporal resolution. Firstly, the FRET ordinary Pluronic micelles (OPMs) and disulfide bond crosslinked Pluronic micelles (CPMs) were synthesized to quantify their integrity in vitro and in vivo by FRET ratio. The behaviors and integrity of OPMs and CPMs in vivo were visually investigated in zebrafish larvae across the entire living organism and at cellular molecular level after intravenous microinjection. Results showed that OPMs were rapidly disassociated in circulation, then largely sequestrated by the endothelial cells (ECs) of caudal vein (CV) and liver in zebrafish larvae, which resulted in quick elimination from blood circulation. While the CPMs were more stable and escaped the sequestration by ECs of CV and liver, which prolonged their circulation in blood. Moreover, we pioneered to use the zebrafish model to reveal that polymeric micelles were eliminated through hepatobiliary pathway after disassociation. While the intact micelles were relatively difficult to eliminate. We further verified that the scavenger receptors of ECs but not the macrophages mainly mediated the elimination of polymeric micelles in CV and liver of zebrafish larvae. These finding on behaviors and elimination mechanisms of polymeric micelles in zebrafish model could contribute to the rational design and optimization of nanomedicines, further guide their studies in rodents.

Highly Transparent, Highly Thermally Stable Nanocellulose/Polymer Hybrid Substrates for Flexible OLED Devices.

Flexible organic light-emitting diode (OLED) devices based on polymer substrates have attracted worldwide attention. However, the current OLED polymer substrates are limited due to weak thermal stability, which is not compatible with the high temperature in OLED fabrication. Here, we developed a novel nanocellulose/polyarylate (PAR) hybrid polymer substrate with both high transparency and excellent thermal properties. Benefiting from the nanometer scale of the cellulose nanofibrils (CNFs) and the efficient interfacial interaction with PAR, the substrate exhibited greatly improved thermal stability, with a glass transition temperature of 192 °C, the thermal decomposition temperature of 501 °C, and upper operating temperature up to over 220 °C. Meanwhile, the hybrid substrate exhibits outstanding mechanical properties. Notably, no apparent transparency loss was observed after the CNF addition, and the hybrid substrate maintains a high transmittance of 85% and a low haze of 1.75%@600 nm. Moreover, OLED devices fabricated on the hybrid substrates exhibit a much improved optoelectrical performance than that of the devices fabricated on the conventional poly(ethylene terephthalate) (PET) substrates. We anticipate this research will open up a new route for fabricating flexible high-performance OLEDs.

Binding Conductive Ink Initiatively and Strongly: Transparent and Thermally Stable Cellulose Nanopaper as a Promising Substrate for Flexible Electronics.

For flexible electronics, the substrates play key roles in ensuring their performance. However, most substrates suffer from weak bonding with the conductive ink and need additional aids. Here, inspired by the Ag-S bond theory, a novel cellulose nanopaper substrate is presented to improve the bond strength with the Ag nanoparticle ink through a facile printing method. The substrate is fabricated using thiol-modified nanofibrillated cellulose and exhibits excellent optical properties (∼85%@550 nm), ultra-small surface roughness (3.47 nm), and high thermal dimensional stability (up to at least 90 °C). Most importantly, it can attract Ag nanoparticles initiatively and bind them firmly, which enable the conductive ink to be printed without using the ink binder and form a strong substrate-ink bonding and maintain a stable conductivity of 2 × 10-4 Ω cm even after extensive peeling and bending. This work may lead to exploring new opportunities to fabricate high-performance flexible electronics using the newly developed nanopaper substrate.

NPC1L1-Targeted Cholesterol-Grafted Poly(ß-Amino Ester)/pDNA Complexes for Oral Gene Delivery.

Gene vectors for oral delivery encounter harsh conditions throughout the gastrointestinal tract, and the continuous peristaltic activity can quickly remove the vectors, leading to inefficient intestinal permeation. Therefore, vectors have demanding property requirements, such as stability under various pH and, more importantly, efficient uptake in different intestinal segments. In this study, a functional polymer, cholesterol-grafted poly(ß-amino ester) (poly[hexamethylene diacrylate-ß-(5-amino-1-pentanol)] (CH-PHP)), is synthesized and electrostatically interacted with plasmid DNA to form a CH-PHP/DNA complex (CPNC). This complex is designed to target the Niemann-Pick C1-like receptor, a cholesterol receptor, to improve oral gene delivery efficacy. With the presence of cholesterol, CH-PHP shows mitigated cytotoxicity, enhanced enzyme resistance, and improved gene condensing ability. CPNC further contributes to ≈43.1- and 2.3-fold increases in luciferase expression in Caco-2 cells compared with PNC and Lipo 2000/DNA complexes, respectively. In addition, the in vivo transfection efficacy of CPNC is ≈4.1-, 2.1-, and 1.6-fold higher than that of Lipo 2000/DNA complexes in rat duodenum, jejunum, and ileum, respectively. Therefore, CPNC may be a promising delivery vector for gene delivery, and using a cholesterol-specific endocytic pathway can be a novel approach to achieve efficient oral gene transfection.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles.

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. This review introduces the application of FNP to produce poorly water-soluble drug nanoparticles by controllable mixing devices, such as confined impinging jets mixer (CIJM), multi-inlet vortex mixer (MIVM) and many other microfluidic mixer systems. The formation mechanisms and processes of drug nanoparticles by FNP are described in detail. Then, the controlling of supersaturation level and mixing rate during the FNP process to tailor the ultrafine drug nanoparticles as well as the influence of drugs, solvent, anti-solvent, stabilizers and temperature on the fabrication are discussed. The ultrafine and uniform nanoparticles of poorly water-soluble drug nanoparticles prepared by CIJM, MIVM and microfluidic mixer systems are reviewed briefly. We believe that the application of microfluidic mixing devices in laboratory with continuous process control and good reproducibility will be benefit for industrial formulation scale-up.

A panel of seven-miRNA signature in plasma as potential biomarker for colorectal cancer diagnosis.

Colorectal cancer (CRC) has been one of the most commonly diagnosed cancers in global. The differential expression profiles of microRNAs (miRNAs) in CRC plasma of patients have the potential to serve as a diagnostic biomarker. We conducted a four-stage study to identify the potential plasma miRNAs for CRC detection. In the initial screening phase, Exiqon panel (miRCURY-Ready-to-Use-PCR-Human-panel-I + II-V1.M) including 3 CRC pools and 1 normal controls (NCs) pool were applied to acquire miRNA profiles. In the training stage (30 CRC VS. 30 NCs) and testing stage (79 CRC VS. 76 NCs), quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to conduct candidate miRNA profiles. Then the identified miRNAs were verified in external validation stage (30 CRC VS. 26 NCs). Expression levels of identified miRNAs were assessed in tissue samples (24 pairs) and plasma exosomes (18 CRC VS. 18 NCs). Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic accuracy. Seven miRNAs (miR-103a-3p, miR-127-3p, miR-151a-5p, miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p) were significantly overexpressed in CRC compared with NCs. Area under the ROC curve of the seven-miRNA signature was 0.762, 0.824 and 0.895 for the training, testing and the external validation stages, respectively. Additionally, miR-103a-3p, miR-127-3p, miR-17-5p and miR-18a-5p were discovered significantly up-regulated in CRC tissues; while miR-17-5p, miR-181a-5p, miR-18a-5p and miR-18b-5p were significantly elevated in CRC plasma exosomes. In conclusion, we established a seven-miRNA signature in the peripheral plasma for CRC detection.

SnS hollow nanofibers as anode materials for sodium-ion batteries with high capacity and ultra-long cycling stability.

In this study, a novel anode material of SnS hollow nanofibers (SnS HNFs) was rationally synthesized by a facile process and demonstrated to be a promising anode candidate for sodium-ion batteries. The synergetic effect of unique hollow and porous microstructures of SnS HNFs led to high capacity and ultra-long cycling stability.

MiR-216a accelerates proliferation and fibrogenesis via targeting PTEN and SMAD7 in human cardiac fibroblasts.

BACKGROUND: Heart failure (HF) is a progressive disease with relatively poor prognosis and lacks effective therapy, and the discovery of dysregulated microRNAs (miRNAs) and their role in cardiac fibroblasts have provided a new avenue for elucidating the mechanism involved in HF. METHODS: Two datasets of GSE53080 and GSE57338 were used to screen the miRNAs profiling and analysis the differentially expressed genes (DEGs) in HF. QRT-PCR was used to detect miR-216a between HF and healthy controls (HC). Cell counting kit-8 (CCK-8) assay and clonogenic assay were used to analyze the effect of proliferation and fibrogenesis. Then dual-luciferase activity assay and western blotting were used to confirm the key mechanism. RESULTS: In this study, the results showed that miR-216a was significantly up-regulated in HF and over-expression of miR-216a promoted proliferation and enhanced the fibrogenesis in the human cardiac fibroblasts (HCF) cells. Phosphatase and tensin homolog (PTEN) and mothers against decapentaplegic homolog 7 (SMAD7) were both validated as the direct target genes of miR-216a, which were confirmed by the dual-luciferase reporter assay. MiR-216a decreased the expression of PTEN and SMAD7 leading to the activation of Akt/mTOR and TGF-ßRI/Smad2 in the HCF cells, which might act as a promoter of cardiac fibrosis. CONCLUSIONS: Our study might provide a promising approach for the treatment of HF in the future.

Electrospun Kraft Lignin/Cellulose Acetate-Derived Nanocarbon Network as an Anode for High-Performance Sodium-Ion Batteries.

An innovative nanocarbon network material was synthesized from electrospun kraft lignin and cellulose acetate blend nanofibers after carbonization at 1000 °C in a nitrogen atmosphere, and its electrochemical performance was evaluated as an anode material in sodium-ion batteries. Apart from its unique network architecture, introduced carbon material possesses high oxygen content of 13.26%, wide interplanar spacing of 0.384 nm, and large specific surface area of 540.95 m2·g-1. The electrochemical test results demonstrate that this new nanocarbon network structure delivers a reversible capacity of 340 mA h·g-1 at a current density of 50 mA·g-1 after 200 cycles and exhibits a high rate capacity by delivering a capacity of 103 mA h·g-1 at an increased current density of 400 mA·g-1. The present work rendered an innovative approach for preparing nanocarbon materials for energy-storage applications and could open up new avenues for novel nanocarbon fabrication from green and environmentally friendly raw materials.

Self-Assembled Core-Shell-Type Lipid-Polymer Hybrid Nanoparticles: Intracellular Trafficking and Relevance for Oral Absorption.

Lipid-polymer hybrid nanoparticles (NPs) are advantageous for drug delivery. However, their intracellular trafficking mechanism and relevance for oral drug absorption are poorly understood. In this study, self-assembled core-shell lipid-polymer hybrid NPs made of poly(lactic-co-glycolic acid) (PLGA) and various lipids were developed to study their differing intracellular trafficking in intestinal epithelial cells and their relevance for oral absorption of a model drug saquinavir (SQV). Our results demonstrated that the endocytosis and exocytosis of hybrid NPs could be changed by varying the kind of lipid. A glyceride mixture (hybrid NPs-1) decreased endocytosis but increased exocytosis in Caco-2 cells, whereas the phospholipid (E200) (hybrid NPs-2) decreased endocytosis but exocytosis was unaffected as compared with PLGA nanoparticles. The transport of hybrid NPs-1 in cells involved various pathways, including caveolae/lipid raft-dependent endocytosis, and clathrin-mediated endocytosis and macropinocytosis, which was different from the other groups of NPs that involved only caveolae/lipid raft-dependent endocytosis. Compared with that of the reference formulation (nanoemulsion), the oral absorption of SQV-loaded hybrid NPs in rats was poor, probably due to the limited drug release and transcytosis of NPs across the intestinal epithelium. In conclusion, the intracellular processing of hybrid NPs in intestinal epithelia can be altered by adding lipids to the NP. However, it appears unfavorable to use PLGA-based NPs to improve oral absorption of SQV compared with nanoemulsion. Our findings will be essential in the development of polymer-based NPs for the oral delivery of drugs with the purpose of improving their oral absorption.