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1.
J Colloid Interface Sci ; 581(Pt A): 185-194, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32771730

RESUMO

Biomimetic nanomaterials have attracted tremendous research interest in the past decade. We recently developed biomimetic core-shell nanoparticles - silica nanocapsules, using a designer dual-functional peptide SurSi under room temperature, neutral pH and without use of any toxic reagents or chemicals. The SurSi peptide is designed capable of not only stabilizing nanoemulsions because of its excellent surface activity, but also inducing the formation of silica through biosilicification at an oil-water interface. However, it remains challenging to precisely control the peptide-induced nucleation and biosilicification specifically at the oil-water interface, thus forming oil-core silica-shell nanocapsules with uniform size and monodispersity. In this study, the fundamental mechanism of silica formation through a peptide catalyzed biosilicification was systematically investigated, so that the formation of oil-core silica-shell nanocapsules can be precisely controlled. The SurSi peptide induced hydrolysis and nucleation of biomineralized silica particles were monitored to study the biosilicification kinetics. Effects of pH, SurSi peptide concentration and pre-hydrolysis of silica precursors were also studied to optimize the formation of biomimetic silica nanocapsules. The fundamental understanding achieved through these systematic studies provides valuable insights for making core-shell nanoparticles via controlling nucleation and reaction at interfaces.

2.
J Adolesc Health ; 67(5S): S48-S54, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33246533

RESUMO

PURPOSE: Children who are left behind when their parents migrate for work have a high prevalence of emotional and behavioral problems, which affect social function and increase family burden. To date, no national survey has been conducted on the emotional and behavioral problems of left-behind children (LBC) in China. This study aimed to investigate the emotional and behavioral outcomes of primary school LBC in the fourth grade in impoverished rural China and the possible influences of family environment and parenting practices. METHODS: A cross-sectional study was carried out in 27 rural counties in the central and western parts of China from November 2016 to January 2017. The method of quota sampling was adopted to achieve a representative sample using postweighting adjustment. The survey sample was distributed proportionately across each county. LBC were defined as children aged <16 years who had two parents leave home to work or one parent leave home while the other lost the capacity to rear their children. The term "non-left-behind children" (NLBC) refers to children who have at least one parent who has not migrated for work. The Strengths and Difficulty Questionnaire (SDQ) was applied to measure children's emotional and behavioral problems. RESULTS: After the weighted calculations were performed, there were 1,147 LBC and 3,953 NLBC. The proportion of abnormal SDQ total scores (>17) was significantly higher in the LBC group than in the NLBC group (15.6% vs. 11.6%; p < .01). Binary regression analysis showed that high levels of insomnia (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.04-2.27), loneliness (OR 1.65, 95% CI 1.13-2.43), and self-harm (OR 1.92, 95% CI 1.17-3.16) may increase the risk of abnormal SDQ total scores in LBC. CONCLUSIONS: LBC showed a higher prevalence of abnormal SDQ total scores than NLBC. Insomnia, loneliness, and self-harm behavior were associated with abnormal SDQ total scores in LBC.

3.
J Colloid Interface Sci ; 584: 528-538, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33129162

RESUMO

Many uses of emulsion droplets require precise control over droplet size and shape. Here we report a 'shape-memorable' micro-droplet formulation stabilized by a polyethylene glycol (PEG)-modified protein -surfactant, the droplets are stable against coalescence for months and can maintain non-spherical shapes for hours, depending on the surface coverage of PEGylated protein. Monodisperse droplets with aspect ratios ranging from 1.0 to 3.4 were controllably synthesized with a flow-focusing microfluidic device. Mechanical properties of the interfacial protein network were explored to elucidate the mechanism behind the droplet shape conservation phenomenon. Characterization of the protein film revealed that the presence of a PEG layer at interfaces alters the mechanical responses of the protein film, resulting in interfacial networks with improved strength. Taking advantage of the prolonged stabilization of non-spherical droplets, we demonstrate functionalization of the droplet interface with accessible biotins. The stabilization of micro-droplet shape with surface-active proteins that also serve as an anchor for integrating functional moieties, provides a tailorable interface for diverse biomimetic applications.

4.
Chempluschem ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894011

RESUMO

Nanoparticles with diverse structures and unique properties have attracted increasing attention for their widespread applications. Co-precipitation under rapid mixing is an effective method to obtained biocompatible nanoparticles and diverse particle carriers are achieved by controlled phase separation via interfacial tensions. In this Minireview, we summarize the underlying mechanism of co-precipitation and show that rapid mixing is important to ensure co-precipitation. In the binary polymer system, the particles can form four different morphologies, including occluded particle, core-shell capsule, dimer particle, and heteroaggregate, and we demonstrate that the final morphology could be controlled by surface tensions through surfactant, polymer composition, molecular weight, and temperature. The applications of occluded particles, core-shell capsules and dimer particles prepared by co-precipitation or microfluidics upon the regulation of interfacial tensions are discussed in detail, and show great potential in the areas of functional materials, colloidal surfactants, drug delivery, nanomedicine, bio-imaging, displays, and cargo encapsulation.

5.
Chempluschem ; 85(9): 2143-2157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32864902

RESUMO

Formulating drugs into nanoparticles offers many attractive advantages over free drugs including improved bioavailability, minimized toxic side effects, enhanced drug delivery, feasibility of incorporating other functions such as controlled release, imaging agents for imaging, targeting delivery, and loading more than one drug for combination therapies. One of the key parameters is drug loading, which is defined as the mass ratio of drug to drug-loaded nanoparticles. Currently, most nanoparticle systems have relatively low drug loading (<10 wt%), and developing methods to increase drug loading remains a challenge. This Minireview presents an overview of recent research on developing nanoparticles with high drug loading (>10 wt%) from the perspective of synthesis strategies, including post-loading, co-loading, and pre-loading. Based on these three different strategies, various nanoparticle systems with different materials and drugs are summarized and discussed in terms of their synthesis methods, drug loadings, encapsulation efficiencies, release profiles, stabilities, and their applications in drug delivery. The advantages and disadvantages of these strategies are presented with an objective of providing useful design rules for future development of high-drug-loading nanoparticles.

6.
Channels (Austin) ; 14(1): 326-335, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32988261

RESUMO

Ca2+-induced Ca2+ release (CICR) from sarcoplasmic reticulum is a finely tuned process responsible for cardiac excitation and contraction. The ubiquitin-proteasome system (UPS) as a major degradative system plays a crucial role in the maintenance of Ca2+ homeostasis. The E3 component N-recognin (UBR) subfamily is a part of the UPS; however, the role of UBR in regulating cardiac CICR is unknown. In the present study, we found that among the UBR family, single knockdown of UBR3 or UBR6 significantly elevated the amplitude of sarcoplasmic reticulum Ca2+ release without affecting Ca2+ transient decay time in neonatal rat ventricular myocytes. The protein expression of alpha 1 C subunit of L-type voltage-dependent Ca2+ channel (Cav1.2) was increased after UBR3/6 knockdown, whereas the protein levels of RyR2, SERCA2a, and PLB remained unchanged. In line with the increase in Cav1.2 proteins, the UBR3/6 knockdown enhanced the current of Cav1.2 channels. Furthermore, the increase in Cav1.2 proteins caused by UBR3/6 reduction was not counteracted by a protein biosynthesis inhibitor, cycloheximide, suggesting a degradative regulation of UBR3/6 on Cav1.2 channels. Our results indicate that UBR3/6 modulates cardiac CICR via targeting Cav1.2 protein degradation.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32743867

RESUMO

Understanding drug-release kinetics is critical for the development of drug-loaded nanoparticles. We developed a J-aggregate-based Förster-resonance energy-transfer (FRET) method to investigate the release of novel high-drug-loading (50 wt %) nanoparticles in comparison with low-drug-loading (0.5 wt %) nanoparticles. Single-dye-loaded nanoparticles form J-aggregates because of the high dye-loading (50 wt %), resulting in a large red-shift (≈110 nm) in the fluorescence spectrum. Dual-dye-loaded nanoparticles with high dye-loading using FRET pairs exhibited not only FRET but also a J-aggregate red-shift (116 nm). Using this J-aggregate-based FRET method, dye-core-polymer-shell nanoparticles showed two release processes intracellularly: the dissolution of the dye aggregates into dye molecules and the release of the dye molecules from the polymer shell. Also, the high-dye-loading nanoparticles (50 wt %) exhibited a slow release kinetics in serum and relatively quick release in cells, demonstrating their great potential in drug delivery.

8.
Nat Commun ; 11(1): 4192, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32826886

RESUMO

Bioluminescence imaging has been widely used in life sciences and biomedical applications. However, conventional bioluminescence imaging usually operates in the visible region, which hampers the high-performance in vivo optical imaging due to the strong tissue absorption and scattering. To address this challenge, here we present bioluminescence probes (BPs) with emission in the second near infrared (NIR-II) region at 1029 nm by employing bioluminescence resonance energy transfer (BRET) and two-step fluorescence resonance energy transfer (FRET) with a specially designed cyanine dye FD-1029. The biocompatible NIR-II-BPs are successfully applied to vessels and lymphatics imaging in mice, which gives ~5 times higher signal-to-noise ratios and ~1.5 times higher spatial resolution than those obtained by NIR-II fluorescence imaging and conventional bioluminescence imaging. Their capability of multiplexed imaging is also well displayed. Taking advantage of the ATP-responding character, the NIR-II-BPs are able to recognize tumor metastasis with a high tumor-to-normal tissue ratio at 83.4.


Assuntos
Trifosfato de Adenosina/metabolismo , Medições Luminescentes/métodos , Metástase Neoplásica/diagnóstico por imagem , Imagem Óptica/métodos , Animais , Técnicas Biossensoriais , Linhagem Celular Tumoral , Feminino , Transferência Ressonante de Energia de Fluorescência/instrumentação , Transferência Ressonante de Energia de Fluorescência/métodos , Xenoenxertos , Humanos , Medições Luminescentes/instrumentação , Camundongos , Imagem Óptica/instrumentação , Neoplasias Ovarianas/diagnóstico por imagem
9.
Small ; 16(30): e2002716, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32578400

RESUMO

Co-precipitation is generally refers to the co-precipitation of two solids and is widely used to prepare active-loaded nanoparticles. Here, it is demonstrated that liquid and solid can precipitate simultaneously to produce hierarchical core-shell nanocapsules that encapsulate an oil core in a polymer shell. During the co-precipitation process, the polymer preferentially deposits at the oil/water interface, wetting both the oil and water phases; the behavior is determined by the spreading coefficients and driven by the energy minimization. The technique is applicable to directly encapsulate various oil actives and avoid the use of toxic solvent or surfactant during the preparation process. The obtained core-shell nanocapsules harness the advantage of biocompatibility, precise control over the shell thickness, high loading capacity, high encapsulation efficiency, good dispersity in water, and improved stability against oxidation. The applications of the nanocapsules as delivery vehicles are demonstrated by the excellent performances of natural colorant and anti-cancer drug-loaded nanocapsules. The core-shell nanocapsules with a controlled hierarchical structure are, therefore, ideal carriers for practical applications in food, cosmetics, and drug delivery.

10.
Sci Adv ; 6(16): eaaz4316, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32426455

RESUMO

The ability of cells to sense external mechanical cues is essential for their adaptation to the surrounding microenvironment. However, how nanoparticle mechanical properties affect cell-nanoparticle interactions remains largely unknown. Here, we synthesized a library of silica nanocapsules (SNCs) with a wide range of elasticity (Young's modulus ranging from 560 kPa to 1.18 GPa), demonstrating the impact of SNC elasticity on SNC interactions with cells. Transmission electron microscopy revealed that the stiff SNCs remained spherical during cellular uptake. The soft SNCs, however, were deformed by forces originating from the specific ligand-receptor interaction and membrane wrapping, which reduced their cellular binding and endocytosis rate. This work demonstrates the crucial role of the elasticity of nanoparticles in modulating their macrophage uptake and receptor-mediated cancer cell uptake, which may shed light on the design of drug delivery vectors with higher efficiency.

11.
Colloids Surf B Biointerfaces ; 193: 111108, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32408256

RESUMO

Biomineralization of metal organic frameworks (MOFs) using biomolecules has recently attracted significant interest because of the benign process including room temperature, neutral pH and without the requirement of any other chemical reagents. Also, these biomolecule incorporated MOFs (biomolecules@MOFs) have demonstrated their potential in biomolecule encapsulation, protection and controlled release. This work aims to develop a general strategy to make biomolecules@MOFs via a biomimetic mineralization process. A library of biomolecules (peptides and proteins) with different charges were systematically studied to fundamentally understand the role of biomolecules and their proprieties in biomolecule-mediated MOF biomineralization. Biomolecule charge, amino acid sequence and stirring speed have been demonstrated to play important roles in controlling biomineralization reaction rate, particle shape and morphology.

12.
Chembiochem ; 21(20): 2871-2879, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32346939

RESUMO

Among various drug-delivery systems, core-shell nanoparticles have many advantages. Inspired by nature, biomimetic synthesis has emerged as a new strategy for making core-shell nanoparticles in recent years. Biomimetic mineralization is the process by which living organisms produce minerals based on biomolecule templating that leads to the formation of hierarchically structured organic-inorganic materials. In this minireview, we mainly focus on the synthesis of core-shell nanoparticle drug-delivery systems by biomimetic mineralization. We review various biomimetic mineralization methods for fabricating core-shell nanoparticles including silica-based, calcium-based and other nanoparticles, and their applications in drug delivery. We also summarize strategies for drug loading in the biomolecule-mineralized core-shell NPs. Current challenges and future directions are also discussed.

13.
Int J Pharm ; 581: 119291, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32259638

RESUMO

Ketamine in sub-anaesthetic doses is an analgesic adjuvant with a morphine-sparing effect. Co-administration of a strong opioid with an analgesic adjuvant such as ketamine is a potential treatment option, especially for patients with cancer-related pain. A limitation of ketamine is its short in vivo elimination half-life. Hence, our aim was to develop biocompatible and biodegradable ketamine-loaded poly(ethylene glycol) (PEG)-block-poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release. Ketamine-encapsulated single polymer PEG-PLGA nanoparticles and double polymer PEG-PLGA/shellac (SH) nanoparticles with a high drug loading of 41.8% (drug weight/the total weight of drug-loaded nanoparticles) were prepared using a new sequential nanoprecipitation method. These drug-loaded nanoparticles exhibited a sustained-release profile for up to 21 days in vitro and for more than 5 days after intravenous injection in mice. Our study demonstrates that high drug loading and a sustained release profile can be achieved with ketamine-loaded PEG-PLGA nanoparticles prepared using this new nanoprecipitation method.

14.
Int J Cancer ; 147(6): 1519-1527, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32010970

RESUMO

Hepatocellular carcinoma (HCC) is the most common type of primary tumor in the liver and is a leading cause of cancer-related death worldwide. Activated hepatic stellate cells (HSCs) are key components of the HCC microenvironment and play an important role in the onset and progression of HCC through the secretion of growth factors and cytokines. Current treatment modalities that include chemotherapy, radiotherapy and ablation are able to activate HSCs and remodel the tumor microenvironment. Growing evidence has demonstrated that the complex interaction between activated HSCs and tumor cells can facilitate cancer chemoresistance and metastasis. Therefore, therapeutic targeting of activated HSCs has emerged as a promising strategy to improve treatment outcomes for HCC. This review summarizes the molecular mechanisms of HSC activation triggered by treatment modalities, the function of activated HSCs in HCC, as well as the crosstalk between tumor cells and activated HSCs. Pathways of activated HSC reduction are discussed, including inhibition, apoptosis, and reversion to the inactivated state. Finally, we outline the progress and challenges of therapeutic approaches targeting activated HSCs in the development of HCC treatment.

15.
Heliyon ; 5(8): e02277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31440604

RESUMO

Various pesticide nanocarriers have been developed. However, their pest-control applications remain limited in laboratories. Herein, we developed silica nanocapsules encapsulating fipronil (SNC) and their engineered form, poly(ethyleneimine)-coated SNC (SNC-PEI), based on recombinant catalytic modular protein D4S2 and used them against termite colonies Coptotermes lacteus in fields. To achieve this, an integrated biomolecular bioprocess was developed to produce D4S2 for manufacturing SNC containing fipronil with high encapsulation efficiency of approximately 97% at benign reaction conditions and at scales sufficient for the field applications. PEI coating was achieved via electrostatic interactions to yield SNC-PEI with a slower release of fipronil than SNC without coating. As a proof-of-concept, bait toxicants containing varied fipronil concentrations were formulated and exposed to nine termite mounds, aiming to prolong fipronil release hence allowing sufficient time for termites to relocate the baits into and distribute throughout the colony, and to eliminate that colony. Some baits were relocated into the mounds, but colonies were not eliminated due to several reasons. We caution others interested in producing bait toxicants to be aware of the multilevel resistance mechanisms of the Coptotermes spp. "superorganism".

16.
Angew Chem Int Ed Engl ; 58(40): 14357-14364, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31364258

RESUMO

A large range of nanoparticles have been developed to encapsulate hydrophobic drugs. However, drug loading is usually less than 10 % or even 1 %. Now, core-shell nanoparticles are fabricated having exceptionally high drug loading up to 65 % (drug weight/the total weight of drug-loaded nanoparticles) and high encapsulation efficiencies (>99 %) based on modular biomolecule templating. Bifunctional amphiphilic peptides are designed to not only stabilize hydrophobic drug nanoparticles but also induce biosilicification at the nanodrug particle surface thus forming drug-core silica-shell nanocomposites. This platform technology is highly versatile for encapsulating various hydrophobic cargos. Furthermore, the high drug loading nanoparticles lead to better in vitro cytotoxic effects and in vivo suppression of tumor growth, highlighting the significance of using high drug-loading nanoparticles.

17.
ACS Nano ; 13(7): 7410-7424, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31287659

RESUMO

The physicochemical properties of nanoparticles play critical roles in regulating nano-bio interactions. Whereas the effects of the size, shape, and surface charge of nanoparticles on their biological performances have been extensively investigated, the roles of nanoparticle mechanical properties in drug delivery, which have only been recognized recently, remain the least explored. This review article provides an overview of the impacts of nanoparticle mechanical properties on cancer drug delivery, including (1) basic terminologies of the mechanical properties of nanoparticles and techniques for characterizing these properties; (2) current methods for fabricating nanoparticles with tunable mechanical properties; (3) in vitro and in vivo studies that highlight key biological performances of stiff and soft nanoparticles, including blood circulation, tumor or tissue targeting, tumor penetration, and cancer cell internalization, with a special emphasis on the underlying mechanisms that control those complicated nano-bio interactions at the cellular, tissue, and organ levels. The interesting research and findings discussed in this review article will offer the research community a better understanding of how this research field evolved during the past years and provide some general guidance on how to design and explore the effects of nanoparticle mechanical properties on nano-bio interactions. These fundamental understandings, will in turn, improve our ability to design better nanoparticles for enhanced drug delivery.

18.
Lab Chip ; 19(12): 2089-2095, 2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-31111136

RESUMO

Natural colorants, which impart a vivid color to food and add additional health benefits, are favored over synthetic colorants; however, their applications are limited by their low solubility in water and low stability. Here, we develop a versatile microfluidic strategy to incorporate natural colorants in shellac nanoparticles with controlled physicochemical properties. The rapid mixing in the microfluidic channels ensures that the mixing time is shorter than the aggregation time, thus providing control over the co-precipitation of the colorant and the polymer. By introducing molecular interactions, colorant nanoaggregates are efficiently embedded in the polymer matrix, forming hierarchical colorant-loaded nanoparticles. The colorant-loaded nanoparticles dispersed in water are transparent and stable over a wide pH range and their polymer matrix also provides a favorable microenvironment that greatly improves the shelf life of the colorants. The improved solubility, stability and bioavailability of the natural colorants suggest that shellac nanoparticles are ideal carriers and the stable, transparent dispersions of biocompatible colorant-loaded nanoparticles in water are well-suited for the development of functional foods, such as natural color drinks.

19.
Adv Healthc Mater ; 8(8): e1900015, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30868753

RESUMO

Two principal methods for cancer drug testing are widely used, namely, in vitro 2D cell monolayers and in vivo animal models. In vitro 2D culture systems are simple and convenient but are unable to capture the complexity of biological processes. Animal models are costly, time-consuming, and often fail to replicate human activity. Here a microfluidic tumor-on-a-chip (TOC) model designed for assessing multifunctional liposome cancer targeting and efficacy is presented. The TOC device contains three sets of hemispheric wells with different sizes for tumor spheroid formation and evaluation of liposomes under a controlled flow condition. There is good agreement between time-elapsed tumor targeting of fluorescent liposomes in the TOC model and in in vivo mouse models. Evaluation of the anticancer efficacy of four PTX-loaded liposome formulations shows that compared to 2D cell monolayers and 3D tumor spheroid models, the TOC model better predicts the in vivo anticancer efficacy of targeted liposomes. Lastly, the TOC model is used to assess the effects of flow rates and tumor size on treatment outcome. This study demonstrates that the TOC model provides a convenient and powerful platform for rapid and reliable cancer drug evaluation.

20.
J Colloid Interface Sci ; 539: 497-503, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30611045

RESUMO

Alginate hydrogel particles are promising delivery systems for protein encapsulation and controlled release because of their excellent biocompatibility, biodegradability, and mild gelation process. In this study, a facile microfluidic approach is developed for making uniform core-shell hydrogel microparticles. To address the challenge of protein retention within the alginate gel matrix, poly(ethyleneimine) (PEI)- and chitosan-coated alginate microparticles were fabricated demonstrating improved protein retention as well as controlled release. Furthermore, a model protein ovalbumin was loaded along with delta inulin microparticulate adjuvant into the water-core of the alginate microparticles. Compared to those microparticles with only antigen loaded, the antigen + adjuvant loaded microparticles showed a delayed and sustained release of antigen. This microfluidic approach provides a convenient method for making well-controlled alginate microgel particles with uniform size and controlled properties, and demonstrates the ability to tune the release profiles of proteins by engineering microparticle structure and properties.


Assuntos
Alginatos/síntese química , Preparações de Ação Retardada/química , Técnicas Analíticas Microfluídicas , Microesferas , Ovalbumina/química , Alginatos/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Tamanho da Partícula , Propriedades de Superfície
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