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1.
Sensors (Basel) ; 23(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36991967

RESUMO

This study proposes an electrocardiogram (ECG) signal stitching scheme to detect arrhythmias in drivers during driving. When the ECG is measured through the steering wheel during driving, the data are always exposed to noise caused by vehicle vibrations, bumpy road conditions, and the driver's steering wheel gripping force. The proposed scheme extracts stable ECG signals and transforms them into full 10 s ECG signals to classify arrhythmias using convolutional neural networks (CNN). Before the ECG stitching algorithm is applied, data preprocessing is performed. To extract the cycle from the collected ECG data, the R peaks are found and the TP interval segmentation is applied. An abnormal P peak is very difficult to find. Therefore, this study also introduces a P peak estimation method. Finally, 4 × 2.5 s ECG segments are collected. To classify arrhythmias with stitched ECG data, each time series' ECG signal is transformed via the continuous wavelet transform (CWT) and short-time Fourier transform (STFT), and transfer learning is performed for classification using CNNs. Finally, the parameters of the networks that provide the best performance are investigated. According to the classification accuracy, GoogleNet with the CWT image set shows the best results. The classification accuracy is 82.39% for the stitched ECG data, while it is 88.99% for the original ECG data.


Assuntos
Aprendizado Profundo , Humanos , Arritmias Cardíacas/diagnóstico , Redes Neurais de Computação , Algoritmos , Eletrocardiografia
2.
Opt Express ; 29(14): 21492-21501, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34265935

RESUMO

A perfect metal film with a periodic arrangement of cut-through slits, an anisotropic metallic metamaterial film, mimics a dielectric slab and supports guided electromagnetic waves in the direction perpendicular to the slits. Since the guided Bloch modes exist only below the light line, conventional metallic metamaterial films do not exhibit interesting leaky-wave effects, such as bound states in the continuum and Fano resonances. Here, we introduce metallic metasurface superlattices that include multiple slits in a period and demonstrate that the superlattices support the Fano resonances and bound states in the continuum. We show that the number of Fano resonances and bound states depend on the number of slits in a period of superlattices through rigorous finite element method simulations. Experimental results in microwave region also support the creation of Fano resonance and bound states in the continuum by the increment of the number of slits in a period of superlattices.

3.
Phys Rev Lett ; 126(1): 013601, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33480783

RESUMO

Conventional photonic lattices, such as metamaterials and photonic crystals, exhibit various interesting physical properties that are attributed to periodic modulations in lattice parameters. In this study, we introduce novel types of photonic lattices, namely Fourier-component-engineered metasurfaces, that do not possess the first Fourier harmonic component in the lattice parameters. We demonstrate that these metasurfaces support the continuous high-Q bound states near second stop bands. The concept of engineering Fourier harmonic components in periodic modulations provides a new method to manipulate electromagnetic waves in artificial periodic structures.

4.
Opt Express ; 28(26): 39453-39462, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33379494

RESUMO

In the physical description of photonic lattices, leaky-mode resonance and bound states in the continuum are central concepts. Understanding of their existence conditions and dependence on lattice parameters is of fundamental interest. Primary leaky-wave effects are associated with the second stop band at the photonic lattice Γ point. The pertinent band gap is defined by the frequency difference between the leaky-mode band edge and the bound-state edge. This paper address the polarization properties of the band gaps resident in laterally periodic one-dimensional photonic lattices. We show that the band gaps pertinent to TM and TE leaky modes exhibit significantly differentiated evolution as the lattice parameters vary. This is because the TM band gap is governed by a surface effect due to the discontinuity of the dielectric constant at the interfaces of the photonic lattice as well as by a Bragg effect due to the periodic in-plane dielectric constant modulation. We find that when the lattice is thin (thick), the surface (Bragg) effect dominates the Bragg (surface) effect in the formation of the TM band. This leads to complex TM band dynamics with multiple band closures possible under parametric variation. In complete contrast, the TE band gap is governed only by the Bragg effect thus exhibiting simpler band dynamics. This research elucidates the important effect of polarization on resonant leaky-mode band dynamics whose explanation has heretofore not been available.

5.
Sensors (Basel) ; 20(6)2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32188056

RESUMO

Vehicle wheel alignment inspection is generally carried out using a computer vision-based system. Due to its inspection mechanism using four wheel centers, the computer vision-based system cannot be applied to the wheel alignment inspection of suspension module units. However, when a vehicle suspension module is being developed, there is no complete car ready for wheel alignment inspection even though it is a very important procedure for suspension property tests. This study proposes a novel and efficient way to inspect vehicle wheel alignment for suspension modules. Two laser modules and several mechanical jigs were employed for wheel alignment inspection, allowing the toe and camber angles of the suspension module to be measured. For accurate wheel alignment results, calibration of the laser modules was performed prior to the inspection. This calibration procedure adjusts the yaw and pitch angles of the laser module so that they can be orthogonal to the mounting jig. For the calibration, a novel method of using laser straightness was adopted and, consequently, 0.02 degrees of orthogonality was achieved. The wheel alignment inspection results were determined then verified using a vision system with two cameras. In order to use this vision system, two cameras were used and a new method of modifying the measurement mechanism was developed. According to the verification results, the proposed wheel alignment inspection provided very high measurement accuracy. The wheel alignment inspection mechanism proposed in this study can not only give very reliable results but also provide a cost-efficient method of inspecting the wheel alignment of suspension modules to automakers.

6.
Can J Infect Dis Med Microbiol ; 2020: 8874309, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33488887

RESUMO

Tuberculosis (TB) is an ongoing global health problem, including in South Korea. To manage TB efficiently, it is necessary to understand the epidemiology, transmission route, and characteristics of prevailing Mycobacterium tuberculosis strains. In this study, we investigated microevolutions over time in the spoligotype patterns of M. tuberculosis isolated from TB patients in Korea. We collected 1,055 clinical M. tuberculosis isolates from 16 provinces in Korea from 1994 to 2006 and analyzed them by spoligotyping. We observed 26 subfamilies, including two large predominant families: a Beijing family (72.7%) and the T family (19.1%). Specifically, the abundance of spoligotype SIT269 from the Beijing-like subfamily significantly increased in the 2000s relative to the 1990s in Korea. This study provides an overview of the M. tuberculosis genotype trends over time in Korea. These data also indicate that we should consider the influence of the newly growing SIT269 subtype identified in the Beijing family.

7.
Opt Express ; 22(4): 4050-8, 2014 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-24663726

RESUMO

The propagation characteristics of spoof surface plasmon modes are studied in both real and reciprocal spaces. From the metallic square lattice, we obtain constant frequency contours by directly measuring electric fields in the microwave frequency regime. The anisotropy of the measured constant frequency contour supports the presence of the negative refraction and the self-collimation which are confirmed from measured electric fields. Additionally, we demonstrate the spoof surface plasmon beam splitter in which the splitting ratio of the self-collimated beam is controlled by varying the height of rods.

8.
J Korean Med Sci ; 29(3): 328-33, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24616579

RESUMO

Pertussis is a representative vaccine-preventable disease. However, there have been recent outbreaks in countries where even higher vaccination against the disease. One reason is the emergence of antigenic variants, which are different to vaccine type. In Korea, reported cases have rapidly increased since 2009. Therefore, we analyzed genotype of strains isolated in 2011-2012 by multilocus sequence typing method. As expected, the genotype profiles of tested genes dramatically changed. The major sequence type changed from ST1 to ST2, and new sequence type (ST8) appeared. In the minimum spanning tree, recent isolates belonging to the ACC-I-ST3 subgroup were detected that were composed of ST2, ST3, and ST6. In particular, the ST2 frequency increased to 81%. The novel ST8 was linked to the increased frequency of ST2. In addition, toxic strains carrying the ptxP3 promoter type were confirmed. This ptxP3 type emerged from 2009 and its frequency had increased to 100% in 2012. Based on these results, it can be inferred that the genotypic changes in the currently circulating strains are strongly associated with the recent increasing of pertussis in Korea. Therefore, the surveillance system should be strengthened, and genetic characterization of the isolates should be expanded to the whole genome sequence level.


Assuntos
Variação Antigênica , Antígenos/genética , Bordetella pertussis/genética , Bordetella pertussis/metabolismo , Coqueluche/microbiologia , Antígenos/imunologia , Antígenos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bordetella pertussis/isolamento & purificação , Genes Bacterianos , Genótipo , Humanos , Toxina Pertussis/genética , Toxina Pertussis/metabolismo , Regiões Promotoras Genéticas , República da Coreia , Análise de Sequência de DNA , Coqueluche/imunologia , Coqueluche/patologia
9.
Microbiol Resour Announc ; 12(9): e0131722, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37477439

RESUMO

The genome of Coxiella burnetii KZQ2, isolated from clinical patients in Korea, is 2.04 MB long. Multispacer types were ST77, and phylogenetic tree analysis showed that KZQ2 is closely related to the CbuK_Q154 chronic strain isolated from human endocarditis patients in the USA.

10.
Sci Rep ; 13(1): 6680, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095302

RESUMO

Graphene-based optical modulators have been extensively studied owing to the high mobility and tunable permittivity of graphene. However, weak graphene-light interactions make it difficult to achieve a high modulation depth with low energy consumption. Here, we propose a high-performance graphene-based optical modulator consisting of a photonic crystal structure and a waveguide with graphene that exhibits an electromagnetically-induced-transparency-like (EIT-like) transmission spectrum at terahertz frequency. The high quality-factor guiding mode to generate the EIT-like transmission enhances light-graphene interaction, and the designed modulator achieves a high modulation depth of 98% with a significantly small Fermi level shift of 0.05 eV. The proposed scheme can be utilized in active optical devices that require low power consumption.

11.
Opt Express ; 20(8): 8309-16, 2012 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-22513542

RESUMO

The resonant transmission of self-collimated beams through zigzag-box resonators is demonstrated experimentally and numerically. Numerical simulations show that the flat-wavefront and the width of the beam are well maintained after passing through zigzag-box resonators because the up and the down zigzag-sides prevent the beam from spreading out and the wavefront is perfectly reconstructed by the output zigzag-side of the resonator. Measured split resonant frequencies of two- and three-coupled zigzag-box resonators are well agreed with those predicted by a tight binding model to consider optical coupling between the nearest resonators. Slowing down the speed of self-collimated beams is also demonstrated by using a twelve-coupled zigzag-box resonator in simulations. Our work could be useful in implementing devices to manipulate self-collimated beams in time domain.

12.
Scand J Infect Dis ; 44(3): 168-73, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22074490

RESUMO

BACKGROUND: Slaughterhouse workers are in direct contact with cattle nearly every day. The purpose of this study was to survey the presence and distribution of anti-Shiga toxin 1 (Stx1) immunoglobulin G (IgG) in slaughterhouse workers, enabling a study of the serologic response to this toxin while working in an area at high-risk of Stx-producing Escherichia coli (STEC) infection. METHODS: One thousand seven hundred and twenty-nine serum samples from healthy slaughterhouse employees were collected and surveyed by indirect enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the 5 slaughterhouse positions, slaughterers had the highest distribution of anti-Stx1 IgG values by an ELISA. Based on the ELISA values, 25% (433/1729) of the workers had anti-Stx1 IgG. Slaughterers, residual products handlers, inspectors, livestock hygiene controllers, and grading testers had anti-Stx1 IgG-positive rates of 28%, 25%, 20%, 19%, and 17%, respectively. The ELISA values of anti-Stx1 IgG increased with increases in the number of years worked by slaughterers, but not by residual products handlers, inspectors, livestock hygiene controllers, or grading testers. CONCLUSIONS: From these results, slaughterhouse workers are healthy and asymptomatic; slaughterers in particular are at high-risk for STEC exposure.


Assuntos
Matadouros , Anticorpos Antibacterianos/sangue , Antitoxinas/sangue , Toxina Shiga/imunologia , Escherichia coli Shiga Toxigênica/imunologia , Adulto , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática , Feminino , Experimentação Humana , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional , República da Coreia
13.
J Korean Med Sci ; 26(2): 196-200, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21286009

RESUMO

The morbidity of travelers' diarrhea (TD) is still high. This study examined the incidence of common pathogens and characteristics of TD among Korean travelers who visited South-East Asian countries. We performed a prospective study involving 479 Korean travelers with diarrheal disease from February 2009 to April 2009 and stool samples were examined and questionnaire surveys were done after arrival. Enterotoxigenic Escherichia coli (ETEC) was found in 36.0% of TD cases, as were the following: Enteroaggregative Escherichia coli (EAEC) in 27.0%, Vibrio parahaemolyticus in 13.1%, and Norovirus in 11.5%. The detected rate of classic TD was higher in men (P = 0.007), in patients who had a shorter duration trip (P = 0.023) and in patients who drank more than 1 liter of water per day (P = 0.037). Positive stool culture rates were higher in men (P = 0.005), in hospitalized patients (P = 0.013). and in those who consumed impure water or raw foods (P = 0.033). A higher severity of disease corresponded to a significantly higher culture positivity rate (P = 0.029). We should consider the possibility of other pathogens in addition to ETEC in patients with TD who visit South-East Asia. Travelers need to educate about risk factors associated with TD.


Assuntos
Povo Asiático , Diarreia/etiologia , Viagem , Adolescente , Adulto , Idoso , Sudeste Asiático/epidemiologia , Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Criança , Diarreia/epidemiologia , Diarreia/microbiologia , Diarreia/virologia , Escherichia coli/isolamento & purificação , Escherichia coli/patogenicidade , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Fezes/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norovirus/isolamento & purificação , Norovirus/patogenicidade , Estudos Prospectivos , República da Coreia , Fatores de Risco , Inquéritos e Questionários , Medicina de Viagem , Vibrio parahaemolyticus/isolamento & purificação , Vibrio parahaemolyticus/patogenicidade , Adulto Jovem
14.
Biomater Sci ; 9(21): 7275-7286, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34609388

RESUMO

Hepatocellular carcinoma is the most common malignancy with a high incidence rate and is the leading cause of cancer-related deaths. Herein, we developed a thermo-responsive hydrogel comprising poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) that exhibits acidity-accelerated delivery of the tumor-targeting glucuronic acid-bearing doxorubicin (DOX-pH-GA) conjugate into tumor tissues. The PCLA copolymer was post-modified with boronic acid (BA-PCLA) to covalently cross-link with the pH-responsive DOX-pH-GA conjugate. The BA-PCLA copolymer effectively coordinated with the DOX-pH-GA conjugate through the boronate ester formation and showed a lower critical gelation temperature. The DOX conjugated via boronate ester exhibited a sustained release in vitro. Subcutaneous administration of PCLA copolymers formed in situ gels in the subcutaneous layers of Sprague-Dawley rats and degraded after 6 weeks. Similarly, BA-PCLA copolymers coordinated with DOX-pH-GA formed a stable in situ gel in vivo. In vivo imaging studies demonstrated that DOX-pH-GA was released in a sustained manner. The anti-tumor activity of the DOX releasing injectable hydrogel was examined using a HepG2 liver cancer xenograft model. The in vivo antitumor effect demonstrated that the DOX releasing hydrogel depot remarkably suppresses the tumor growth. These results demonstrate that the pH-responsive DOX releasing thermo-responsive hydrogel depot has great potential for application in localized anticancer therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Ésteres , Hidrogéis , Concentração de Íons de Hidrogênio , Neoplasias Hepáticas/tratamento farmacológico , Ratos , Ratos Sprague-Dawley
15.
Opt Express ; 18(16): 17106-13, 2010 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-20721099

RESUMO

We propose a ring-type Fabry-Pérot filter (RFPF) based on the self-collimation effect in photonic crystals. The transmission characteristics of self-collimated beams are experimentally measured in this structure and compared with the results obtained with the simulations. Bending and splitting mechanisms of light beams by the line defects introduced into the RFPF are used to control the self-collimated beam. Antireflection structures are also employed at the input and output photonic crystal interfaces in order to minimize the coupling loss. Reflectance of the line-defect beam splitters can be controlled by adjusting the radius of defect rods. As the reflectance of the line-defect beam splitters increases, the transmission peaks become sharper and the filter provides a Q-factor as high as 1037. Proposed RFPF can be used as a sharply tuned optical filter or as a spectrum analyzer based on the self-collimation phenomena of photonic crystals. Furthermore, it is suitable for a building block of photonic integrated circuits, as it does not back reflect any of the incoming self-collimated beams owing to the antireflection structure applied.


Assuntos
Simulação por Computador , Filtração/instrumentação , Luz , Fótons , Espalhamento de Radiação , Cristalização/instrumentação , Desenho de Equipamento , Dispositivos Ópticos
16.
Carbohydr Polym ; 233: 115832, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32059885

RESUMO

In the present study, a type of bioconjugate was synthesized by post modification of alginate by conjugating temperature-responsive poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide) and O-phosphorylethanolamine as phosphorylation functional groups. Freely flowing bioconjugate sols at low temperature can transform to stable viscoelastic gels at the physiological temperature (37 °C). Subcutaneous administration of temperature-responsive bioconjugate sols into the dorsal region of Sprague-Dawley rats formed in situ hydrogel. in situ formation of bioconjugate gels in stimulated body fluids at 37 °C showed nucleation and hydroxyapatite mineral growth. Furthermore, hydroxyapatite growth was also found in in vivo gels, which suggested the potential of alginate-based bioconjugate gels as a scaffold for bone engineering. Bone morphogenetic protein 2 (BMP-2)-loaded bioconjugate formed stable gel in vivo, and demonstrated sustained release. BMP-2-loaded bioconjugates exhibited in situ biomineralization in vivo. These results imply that the in situ formation of injectable biomimetic materials has potential for bone tissue engineering applications.


Assuntos
Alginatos/farmacologia , Materiais Biocompatíveis/farmacologia , Biomineralização/efeitos dos fármacos , Hidrogéis/farmacologia , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Alginatos/síntese química , Alginatos/toxicidade , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Proteína Morfogenética Óssea 2/farmacologia , Sistemas de Liberação de Medicamentos , Durapatita/metabolismo , Etanolaminas/química , Células HEK293 , Humanos , Hidrogéis/síntese química , Hidrogéis/toxicidade , Masculino , Transição de Fase , Poliésteres/síntese química , Poliésteres/toxicidade , Polietilenoglicóis/síntese química , Polietilenoglicóis/toxicidade , Ratos Sprague-Dawley , Engenharia Tecidual/métodos
17.
J Control Release ; 324: 532-544, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32454120

RESUMO

Therapeutic proteins are attractive candidates for the treatment of human diseases. However, their short half-life often limits their clinical application. To overcome this problem, injectable hydrogels have been developed as depots for controlled release of therapeutic proteins, but these systems have not yet achieved the desired extended, sustained drug release profile. Our strategy herein was to implement selective and strong interactions between the hydrogels and therapeutic proteins. Specifically, we investigated whether strong and specific interactions between human serum albumin (HSA) and albumin-binding peptide (ABP) can be used to achieve extended release of urate oxidase (Uox), a therapeutic protein for hyperuricemia treatment, from pH- and temperature-sensitive injectable hydrogels consisting of poly(ethylene glycol)-poly(ß-amino ester urethane) (PEG-PAEU) copolymer. Thus, HSA was conjugated to Uox (Uox-HSA) and ABP was introduced in PEG-PAEU (PEG-PAEU-ABP). Polymers, conjugates, and hydrogels were extensively characterized for their physicochemical characteristics and in vivo efficacy in a hyperuricemia mouse model. Briefly, the hydrogels exhibited good injectability, in vitro biocompatibility and extended drug release, and in vivo gel formation and degradability. The serum half-life of the Uox-HSA loaded in PEG-PAEU-ABP hydrogels was ~96 h in mice, which was ~88, ~5.5, and ~2 times longer than that of free native Uox, free Uox-HSA, and Uox-HSA loaded in PEG-PAEU hydrogels, respectively. In the hyperuricemia mouse model, Uox-HSA loaded in PEG-PAEU-ABP hydrogels exhibited a substantially extended period of uric acid-lowering efficacy. These results clearly show that by applying ABP-HSA strong interaction to injectable hydrogels and therapeutic protein, the concentration of the therapeutic protein can be maintained for a long period in vivo, prolonging its therapeutic effect. Further, our approach can be tailored to accommodate other therapeutic proteins, which potentially expands the clinical applicability range of these systems.


Assuntos
Hiperuricemia , Urato Oxidase , Animais , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hidrogéis , Hiperuricemia/tratamento farmacológico , Camundongos , Polietilenoglicóis , Albumina Sérica Humana
18.
Biomaterials ; 230: 119599, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31718883

RESUMO

Cancer vaccines that elicit a robust and durable antitumor response show great promise in cancer immunotherapy. Nevertheless, low immunogenicity and weak immune response limit the application of cancer vaccines. To experience next generation cancer vaccines that elicit robust, durable, and anti-tumor T cell response, herein we design injectable smart hydrogels (ISHs) that self-assemble into a cellular microenvironment-like microporous network using a simple hypodermic needle injection, to localize the immune cells and program host cells. ISHs, composed of levodopa- and poly(ε-caprolactone-co-lactide)ester-functionalized hyaluronic acid (HA-PCLA), are loaded with immunomodulatory factor (OVA expressing plasmid, pOVA)-bearing nano-sized polyplexes and granulocyte-macrophage colony-stimulating factor (GM-CSF) as dendritic cell (DC) enhancement factor. Subcutaneous administration of ISHs effectively localized immune cells, and controlled the delivery of immunomodulatory factors to recruit immune cells. The microporous network allowed the recruitment of a substantial number of DCs, which was 6-fold higher than conventional PCLA counterpart. The locally released nano-sized polyplexes effectively internalized to DCs, resulting in the presentation of tumor-specific OVA epitope, and subsequent activation of CD4+ T cells and generation of OVA-specific serum antibody. By the controlled release of nano-sized polyplexes and GM-CSF through a single subcutaneous injection, the ISHs effectively eliminated B16/OVA melanoma tumors in mice. These ISHs can be administered using a minimal invasive technique that could bypass the need for extracorporeal training of cells ex vivo, and provide sustained release of cancer vaccines for immunomodulation. These important findings suggest that ISHs can serve as powerful biomaterials for cancer immunotherapy.


Assuntos
Vacinas Anticâncer , Hidrogéis , Imunidade Humoral , Neoplasias Pulmonares , Animais , Células Dendríticas/imunologia , Humanos , Pulmão , Neoplasias Pulmonares/terapia , Camundongos , Camundongos Endogâmicos C57BL , Microambiente Tumoral
19.
Biomater Sci ; 7(12): 5424-5437, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638108

RESUMO

Development of implantable material to control the release of chemotherapeutics in the body is a promising approach to control cancer cell proliferation; however, implantation requires surgical intervention. Herein, we propose the in situ formation of injectable biogels (IBGs) for the programmed delivery of potent chemotherapeutic drugs. IBGs are developed via cohesive molecular assembly of a polysaccharide-polymer network comprised of hyaluronic acid-poly(ß-amino urethane). Biocompatible IBGs could be administered subcutaneously through a hypodermic needle in vivo to subsequently assemble into a microporous network. The hyaluronic acid-shielded network mimics the natural extracellular matrix, avoiding rapid degradation of IBGs, with a soft texture and adhesiveness facilitating integration with dermal tissues after subcutaneous implantation. The natural-mimicking architecture confers the IBG network controlled degradation and bioresorbable properties. Subcutaneous administration of IBGs controlled the delivery of a therapeutic agent in a spatio-temporal manner. Therapeutic agents delivered near the tumors in a sustained manner were effectively infiltrated into the thick solid tumors and provide a durable and enhanced anti-tumor response in the B16/OVA melanoma model in vivo. These results indicate that IBGs could be potential medical interventions for the treatment of cancers.


Assuntos
Antineoplásicos/administração & dosagem , Géis/síntese química , Ácido Hialurônico/química , Melanoma/tratamento farmacológico , Poliuretanos/administração & dosagem , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Géis/química , Células HEK293 , Humanos , Concentração de Íons de Hidrogênio , Injeções Subcutâneas , Células MCF-7 , Poliuretanos/química , Poliuretanos/farmacologia , Ratos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Biomaterials ; 195: 100-110, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30623788

RESUMO

Lymphoid organs, which are populated by dendritic cells (DCs), are highly specialized tissues and provide an ideal microenvironment for T-cell priming. However, intramuscular or subcutaneous delivery of vaccine to DCs, a subset of antigen-presenting cells, has failed to stimulate optimal immune response for effective vaccination and need for adjuvants to induce immune response. To address this issue, we developed an in situ-forming injectable hybrid hydrogel that spontaneously assemble into microporous network upon subcutaneous administration, which provide a cellular niche to host immune cells, including DCs. In situ-forming injectable hybrid hydrogelators, composed of protein-polymer conjugates, formed a hydrogel depot at the close proximity to the dermis, resulting in a rapid migration of immune cells to the hydrogel boundary and infiltration to the microporous network. The biocompatibility of the watery microporous network allows recruitment of DCs without a DC enhancement factor, which was significantly higher than that of traditional hydrogel releasing chemoattractants, granulocyte-macrophage colony-stimulating factor. Owing to the sustained degradation of microporous hydrogel network, DNA vaccine release can be sustained, and the recruitment of DCs and their homing to lymph node can be modulated. Furthermore, immunization of a vaccine encoding amyloid-ß fusion proteinbearing microporous network induced a robust antigen-specific immune response in vivo and strong recall immune response was exhibited due to immunogenic memory. These hybrid hydrogels can be administered in a minimally invasive manner using hypodermic needle, bypassing the need for cytokine or DC enhancement factor and provide niche to host immune cells. These findings highlight the potential of hybrid hydrogels that may serve as a simple, yet multifunctional, platform for DNA vaccine delivery to modulate immune response.


Assuntos
Hidrogéis/química , Animais , Fatores Quimiotáticos/metabolismo , Células Dendríticas/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Linfonodos/metabolismo , Vacinação/métodos , Vacinas de DNA/química
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