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1.
J Nanobiotechnology ; 22(1): 30, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38218872

RESUMEN

BACKGROUND: Tumor immunotherapy can not only eliminate the primary lesion, but also produce long-term immune memory, effectively inhibiting tumor metastasis and recurrence. However, immunotherapy also showed plenty of limitations in clinical practice. In recent years, the combination of nanomaterials and immunotherapy has brought new light for completely eliminating tumors with its fabulous anti-tumor effects and negligible side effects. METHODS: The Core Collection of Web of Science (WOSCC) was used to retrieve and obtain relevant literatures on antitumor nano-immunotherapy since the establishment of the WOSCC. Bibliometrix, VOSviewer, CiteSpace, GraphPad Prism, and Excel were adopted to perform statistical analysis and visualization. The annual output, active institutions, core journals, main authors, keywords, major countries, key documents, and impact factor of the included journals were evaluated. RESULTS: A total of 443 related studies were enrolled from 2004 to 2022, and the annual growth rate of articles reached an astonishing 16.85%. The leading countries in terms of number of publications were China and the United States. Journal of Controlled Release, Biomaterials, Acta Biomaterialia, Theranostics, Advanced Materials, and ACS Nano were core journals publishing high-quality literature on the latest advances in the field. Articles focused on dendritic cells and drug delivery accounted for a large percentage in this field. Key words such as regulatory T cells, tumor microenvironment, immune checkpoint blockade, drug delivery, photodynamic therapy, photothermal therapy, tumor-associated macrophages were among the hottest themes with high maturity. Dendritic cells, vaccine, and T cells tend to become the popular and emerging research topics in the future. CONCLUSIONS: The combined treatment of nanomaterials and antitumor immunotherapy, namely antitumor nano-immunotherapy has been paid increasing attention. Antitumor nano-immunotherapy is undergoing a transition from simple to complex, from phenotype to mechanism.


Asunto(s)
Materiales Biocompatibles , Nanoestructuras , Terapia Combinada , Sistemas de Liberación de Medicamentos , Inmunoterapia
2.
Clin Immunol ; 248: 109260, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36791943

RESUMEN

Hand, foot, and mouth disease (HFMD) is a common children infectious disease caused by human enteroviruses. Most of the cases have minimal symptoms, however, some patients may develop serious neurological, cardiac complications, or even death. The pathological mechanism leading to severe HFMD is not clearly understood, and the immunological status of the individual patient may play an important role. Transcriptomes of peripheral blood mononuclear cells from EV71-infected patients (n = 45) and healthy controls (n = 36) were examined. Immune pathways were up-regulated in patients with mild disease symptoms (n = 11, M) compared to the healthy controls (n = 36, H), demonstrating an effective anti-viral response upon EV71 infection. However, in patients with severe symptoms (n = 23, S) as well as severe patients following treatment (n = 11, A), their innate and acquired immune pathways were down-regulated, indicating a global immunity suppression. Such immune suppression characteristics could thus provide an opportunity for early EV-71 infection prognosis prediction. Based on our cohort, an SVM model using RNA-seq expression levels of five genes (MCL1, ZBTB37, PLEKHM1P, IFNAR2 and YEATS2) was developed and achieved a high ROC-AUC (91·3%) in predicting severe HFMD. Meanwhile, qPCR fold-changes method was performed based three genes (MCL1, IFNAR2 and YEATS2) on additional cohort. This qPCR method achieved a ROC-AUC of 78.6% in predicting severe HFMD, which the patients could be distinguished in 2-3 h. Therefore, our models demonstrate the possibility of HFMD severity prediction based on the selected biomarkers that predict severe HFMD effectively.


Asunto(s)
Enterovirus Humano A , Enfermedad de Boca, Mano y Pie , Enfermedades de la Boca , Humanos , Niño , Lactante , Enterovirus Humano A/fisiología , Leucocitos Mononucleares , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Inmunidad Adaptativa , China
3.
Anal Chem ; 95(22): 8487-8495, 2023 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-37216427

RESUMEN

To ensure drinking water quality, the development of rapid and accurate analytical methods is essential. Herein, a highly sensitive electrochemiluminescence (ECL) aptasensor-based on the signal on-off-on strategy was developed to detect the water pollutant microcystin-LR (MC-LR). This strategy was based on a newly prepared ruthenium-copper metal-organic framework (RuCu MOF) as the ECL signal-transmitting probe and three types of PdPt alloy core-shell nanocrystals with different crystal structures as signal-off probes. Compounding the copper-based MOF (Cu-MOF) precursor with ruthenium bipyridyl at room temperature facilitated the retention of the intrinsic crystallinity and high porosity of the MOFs as well as afforded excellent ECL performance. Since bipyridine ruthenium in RuCu MOFs could transfer energies to the organic ligand (H3BTC), the ultra-efficient ligand luminescent ECL signal probe was finally obtained, which greatly improved the sensitivity of the aptasensor. To further improve the sensitivity of the aptasensor, the quenching effects of noble metal nanoalloy particles with different crystal states were investigated, which contained PdPt octahedral (PdPtOct), PdPt rhombic dodecahedral (PdPtRD), and PdPt nanocube (PdPtNC). Among them, the PdPtRD nanocrystal exhibited higher activity and excellent durability, stemming from the charge redistribution caused by the hybridization of Pt and Pd atoms. Moreover, PdPtRD could also load more -NH2-DNA strands because it exposed more active sites with a large specific surface area. The fabricated aptasensor exhibited outstanding sensitivity and stability in MC-LR detection, with a linear detection range of 0.0001-50 ng mL-1. This study provides valuable directions for the application of alloy nanoparticles of noble metals and bimetallic MOFs in the field of ECL immunoassay.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , Rutenio , Estructuras Metalorgánicas/química , Cobre/química , Rutenio/química , Ligandos , Mediciones Luminiscentes/métodos , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Aleaciones , Nanopartículas del Metal/química , Límite de Detección
4.
Nano Lett ; 22(18): 7506-7514, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-36094850

RESUMEN

Here we report the use of defects in ordered solvents to form, manipulate, and characterize individual molecular assemblies of either small-molecule amphiphiles or polymers. The approach exploits nanoscopic control of the structure of nematic solvents (achieved by the introduction of topological defects) to trigger the formation of molecular assemblies and the subsequent manipulation of defects using electric fields. We show that molecular assemblies formed in solvent defects slow defect motion in the presence of an electric field and that time-of-flight measurements correlate with assembly size, suggesting methods for the characterization of single assemblies of molecules. Solvent defects are also used to transport single assemblies of molecules between solvent locations that differ in composition, enabling the assembly and disassembly of molecular "nanocontainers". Overall, our results provide new methods for studying molecular self-assembly at the single-assembly level and new principles for integrated nanoscale chemical systems that use solvent defects to transport and position molecular cargo.


Asunto(s)
Polímeros , Polímeros/química , Solventes/química
5.
J Am Chem Soc ; 143(7): 2622-2637, 2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33560127

RESUMEN

Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five types-eumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelanin-based on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melanin-based materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure-function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.


Asunto(s)
Melaninas/química , Espectroscopía de Resonancia por Spin del Electrón , Indoles/química , Indoles/metabolismo , Espectroscopía de Resonancia Magnética , Melaninas/biosíntesis , Conformación Molecular , Polímeros/química , Polímeros/metabolismo
6.
BMC Cancer ; 21(1): 922, 2021 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-34391381

RESUMEN

OBJECTIVE: Tongue and mouth floor squamous cell carcinoma (T/MF SCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on T/MF SCC remains unclear. MATERIALS AND METHODS: Transcriptome and somatic mutation data of patients with T/MF SCC were obtained from HNSC projects of the Cancer Genome Atlas. Immune infiltration quantification in early- (clinical stage I-II) and advanced-stage (clinical stage III-IV) T/MF SCC was performed using single sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed gene data were filtered, and their function was assessed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Kaplan-Meier survival curve analysis and Cox regression model were conducted to evaluate the survival of patients with the CCL22 signature. Maftools was used to present the overview of somatic mutations. RESULTS: In T/MF SCC, T helper (Th)2 cell counts were significantly increased in patients with early-stage disease compared to those with advanced-stage disease. Expression of the Th2 cell-related chemokine, CCL22, was downregulated in patients with advanced-stage T/MF SCC. Univariate and multivariate Cox analyses revealed that CCL22 was a good prognostic factor in T/MF SCC. A nomogram based on the expression of CCL22 was constructed to serve as a prognostic indicator for T/MF SCC. NOTCH1 mutations were found at a higher rate in patients with advanced-stage T/MF SCC than in those with early-stage T/MF SCC, resulting in the inhibition of the activation of the NOTCH1-Th2 cell differentiation pathway. The expression levels of CCL22, GATA-3, and IL4 were higher in patients with early-stage T/MF SCC than in those with advanced-stage T/MF SCC. CONCLUSION: In T/MF SCC, high expression of CCL22 may promote the recruitment of Th2 cells and help predict a better survival. Mutations in NOTCH1 inhibit the differentiation of Th2 cells, facilitating tumor progression through a decrease in Th2 cell recruitment and differentiation.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/metabolismo , Quimiocina CCL22/genética , Neoplasias de la Boca/etiología , Neoplasias de la Boca/metabolismo , Receptor Notch1/genética , Células Th2/inmunología , Células Th2/metabolismo , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimiotaxis de Leucocito/genética , Quimiotaxis de Leucocito/inmunología , Biología Computacional/métodos , Femenino , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor , Masculino , Persona de Mediana Edad , Suelo de la Boca/metabolismo , Suelo de la Boca/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Mutación , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales
7.
Liver Int ; 41(7): 1498-1508, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33486874

RESUMEN

BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS: Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS: 420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION: NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Antivirales/uso terapéutico , China , ADN Viral , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Recurrencia Local de Neoplasia , Polietilenglicoles/uso terapéutico , Resultado del Tratamiento
8.
J Mater Sci Mater Med ; 32(1): 8, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33471211

RESUMEN

Intervertebral disc (IVD) degeneration is one of the most important causes of lower back pain. Tissue engineering provides a new method for the experimental treatment of degenerative disc diseases. This study aims to develop a natural, acellular, 3D interconnected porous scaffold derived from the extracellular matrix (ECM) of nucleus pulposus. The nucleus pulposus (NP) was decellularized by sequential detergent-nuclease methods, including physical crushing, freeze-drying and cross-linking. These 3D porous scaffolds were fabricated with a high porosity of (81.28 ± 4.10)%, an ideal pore size with appropriate mechanical properties. Rabbit bone marrow mesenchymal stem cells (rBMSCs) were seeded and cultured on the scaffolds. And the mechanical tests showed the compressive elastic modulus of the scaffolds cultured for 4 weeks reached 0.12 MPa, which was better than that of the scaffolds cultured for 2 weeks (0.07 MPa) and that of the control group (0.04 MPa). Scanning electron microscopy (SEM), histological assays, molecular biology assays revealed that the scaffolds could provide an appropriate microstructure and environment for the adhesion, proliferation, migration and secretion of seeded cells in vitro. As assays like histology, immunohistochemistry and the real-time qRT-PCR showed, NP-like tissues were preliminarily formed. In conclusion, the 3D porous scaffold derived from NP ECM is a potential biomaterial for the regeneration of NP tissues. A natural, acellular, 3D interconnected porous scaffold derived from the extracellular matrix (ECM) of nucleus pulposus was developed by sequential detergent-nuclease and freeze-drying method, which can reduce the damage of protein activity to the minimum. It is very similar to the composition and internal environment of the natural nucleus pulposus, because it derived from the natural nucleus pulposus. Scanning electron microscopy (SEM), histological assays, molecular biology assays revealed that the scaffolds could provide an appropriate microstructure and environment for the adhesion, proliferation, migration, and secretion of seeded cells in vitro.


Asunto(s)
Biomimética , Núcleo Pulposo/metabolismo , Animales , Materiales Biocompatibles/metabolismo , Células de la Médula Ósea/citología , Técnicas de Cultivo de Célula , Proliferación Celular , Supervivencia Celular , Matriz Extracelular , Células Madre Mesenquimatosas/citología , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Porosidad , Presión , Conejos , Estrés Mecánico , Sales de Tetrazolio/química , Tiazoles/química , Ingeniería de Tejidos/métodos , Andamios del Tejido
9.
Angew Chem Int Ed Engl ; 60(32): 17464-17471, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-33913253

RESUMEN

Melanosomes in nature have diverse morphologies, including spheres, rods, and platelets. By contrast, shapes of synthetic melanins have been almost entirely limited to spherical nanoparticles with few exceptions produced by complex templated synthetic methods. Here, we report a non-templated method to access synthetic melanins with a variety of architectures including spheres, sheets, and platelets. Three 1,8-dihydroxynaphthalene dimers (4-4', 2-4' and 2-2') were used as self-assembling synthons. These dimers pack to form well-defined structures of varying morphologies depending on the isomer. Specifically, distinctive ellipsoidal platelets can be obtained using 4-4' dimers. Solid-state polymerization of the preorganized dimers generates polymeric synthetic melanins while maintaining the initial particle morphologies. This work provides a new route to anisotropic synthetic melanins, where the building blocks are preorganized into specific shapes, followed by solid-state polymerization.


Asunto(s)
Colorantes/química , Naftoles/química , Polímeros/química , Anisotropía , Colorantes/síntesis química , Naftoles/síntesis química , Polimerizacion , Polímeros/síntesis química
10.
Ecotoxicol Environ Saf ; 203: 111000, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32736119

RESUMEN

Microplastics are identified as a great threat to marine environments. However, knowledge of their impacts on phytoplankton, especially for the diatoms is scarce. Herein, the effects of different polyvinyl chloride (PVC) microplastic concentrations and contact times (24, 48, 72 and 96 h) on the Fv/Fm and cell density of Phaeodactylum tricornutum (B255), Chaetoceros gracilis (B13) and Thalassiosira sp. (B280) were investigated to evaluate the toxic effects of microplastics on marine diatoms. The effects of PVC microplastics on the morphology of the diatoms was observed by SEM. The order of sensitivity to 1 µm PVC microplastics among three marine diatoms was B13 > B280 > B255, showing that the toxic effects varied with different microalgae species. Furthermore, the presence of a siliceous cell wall played a minimal role in protecting cells from the physical attack of PVC microplastics, with no significant difference from the common cell wall. PVC microplastics caused dose-dependent adverse effects on three marine diatoms. High PVC concentrations (200 mg/L) reduced the chlorophyll content, inhibited Fv/Fm, and affected the photosynthesis of three marine diatoms. The PVC microplastics adsorbed and caused physical damage on the structure of algal cells. Interactions between PVC microplastics and diatoms may be the probable reason for the negative effects of PVC on diatoms.


Asunto(s)
Diatomeas/efectos de los fármacos , Microplásticos/toxicidad , Cloruro de Polivinilo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Adsorción , Clorofila/metabolismo , Diatomeas/crecimiento & desarrollo , Diatomeas/fisiología , Relación Dosis-Respuesta a Droga , Microalgas/efectos de los fármacos , Microalgas/crecimiento & desarrollo , Microalgas/fisiología , Fotosíntesis/efectos de los fármacos , Fitoplancton/efectos de los fármacos , Fitoplancton/crecimiento & desarrollo , Fitoplancton/fisiología , Factores de Tiempo
11.
Angew Chem Int Ed Engl ; 59(43): 19136-19142, 2020 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-32659039

RESUMEN

Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide-polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL-1 ) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic "KLA" peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide-polymer conjugates for intracellular delivery.


Asunto(s)
Apoptosis , Luz , Nanopartículas/química , Péptidos/química , Polímeros/química , Secuencia de Aminoácidos , Supervivencia Celular/efectos de los fármacos , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Micelas , Polimerizacion
12.
Bioconjug Chem ; 30(7): 1889-1904, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-30969752

RESUMEN

Over the past decade, the field of polymer-oligonucleotide nanomaterials has flourished because of the development of synthetic techniques, particularly living polymerization technologies, which provide access to polymers with well-defined architectures, precise molecular weights, and terminal or side-chain functionalities. Various "living" polymerization methods have empowered chemists with the ability to prepare functional polymer-oligonucleotide conjugates yielding a library of architectures, including linear diblock, comb, star, hyperbranched star, and gel morphologies. Since oligonucleotides are hydrophilic and synthetic polymers can be tailored with hydrophobicity, these amphiphilic polymer-oligonucleotide conjugates are capable of self-assembling into nanostructures with different shapes, leading to many high-value-added biomedical applications, such as drug delivery systems, gene regulation, and 3D-bioprinting. This review aims to highlight the main living polymerization approaches to polymer-oligonucleotide conjugates, including ring-opening metathesis polymerization, atom transfer radical polymerization (ATRP), reversible addition-fragmentation transfer polymerization (RAFT), and ring-opening polymerization of cyclic esters and N-carboxyanhydride. The self-assembly properties and resulting applications of polymer-DNA hybrid materials are highlighted as well.


Asunto(s)
Nanoestructuras/química , Oligonucleótidos/química , Polimerizacion , Polímeros/química , Tensoactivos/química , Animales , Técnicas de Química Sintética/métodos , Sistemas de Liberación de Medicamentos , Humanos , Nanoestructuras/ultraestructura , Nanotecnología/métodos , Oligonucleótidos/síntesis química , Polímeros/síntesis química , Tensoactivos/síntesis química
13.
Faraday Discuss ; 219(0): 44-57, 2019 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-31549115

RESUMEN

We describe cyclic peptide progelators which cleave in response to UV light to generate linearized peptides which then self-assemble into gel networks. Cyclic peptide progelators were synthesized, where the peptides were sterically constrained, but upon UV irradiation, predictable cleavage products were generated. Amino acid sequences and formulation conditions were altered to tune the mechanical properties of the resulting gels. Characterization of the resulting morphologies and chemistry was achieved through liquid phase and standard TEM methods, combined with matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS).


Asunto(s)
Bioimpresión/métodos , Geles/química , Péptidos Cíclicos/química , Materiales Biocompatibles/química , Fotólisis/efectos de la radiación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Rayos Ultravioleta
14.
Angew Chem Int Ed Engl ; 58(48): 17359-17364, 2019 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-31595626

RESUMEN

Harnessing metal-free photoinduced reversible-deactivation radical polymerization (photo-RDRP) in organic and aqueous phases, we report a synthetic approach to enzyme-responsive and pro-apoptotic peptide brush polymers. Thermolysin-responsive peptide-based polymeric amphiphiles assembled into spherical micellar nanoparticles that undergo a morphology transition to worm-like micelles upon enzyme-triggered cleavage of coronal peptide sidechains. Moreover, pro-apoptotic polypeptide brushes show enhanced cell uptake over individual peptide chains of the same sequence, resulting in a significant increase in cytotoxicity to cancer cells. Critically, increased grafting density of pro-apoptotic peptides on brush polymers correlates with increased uptake efficiency and concurrently, cytotoxicity. The mild synthetic conditions afforded by photo-RDRP, make it possible to access well-defined peptide-based polymer bioconjugate structures with tunable bioactivity.


Asunto(s)
Micelas , Nanopartículas/química , Péptidos/química , Polímeros/química , Termolisina/química , Acrilatos/química , Aminoácidos/química , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Radicales Libres/química , Células HeLa , Humanos , Conformación Molecular , Procesos Fotoquímicos , Polimerizacion , Polimetil Metacrilato/química , Solventes/química , Relación Estructura-Actividad
15.
Proteomics ; 17(9)2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28230319

RESUMEN

Macroporous cryogels were prepared and used to deplete abundant proteins. It was accomplished based on the sample heterogeneity rather than any exogenous assistance. Human serum was added in monomer solutions to synthesize molecularly imprinted polymers; therein some abundant proteins were imprinted in the polyacrylamide cryogels. Meanwhile the rare components remained aqueous. Chromatography and electrophoresis showed that albumin, serotransferrin, and most globulins were depleted by columns packed with the molecularly imprinted polymers. After the depletion, lower abundance proteins were revealed by SDS-PAGE, peptide fingerprint analysis, and identified by MALDI-TOF-MS. This is an example that a "per se imprint" protocol enables to gradually dimidiate proteomes, simplify sample complexities, and facilitate further proteome profiling or biomarker discovery.


Asunto(s)
Proteínas Sanguíneas/química , Proteínas Sanguíneas/aislamiento & purificación , Criogeles/química , Impresión Molecular/métodos , Polímeros/química , Suero/química , Electroforesis en Gel de Poliacrilamida , Humanos , Estructura Molecular
16.
Anal Bioanal Chem ; 409(12): 3245-3251, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28251291

RESUMEN

A sensitive label-free amperometric electrochemical immunosensor for detection of prostate-specific antigen (PSA) was proposed in this work. The nanocomposite of halloysite nanotubes with polypyrrole shell and palladium nanoparticles (HNTs@PPy-Pd) was used as a novel signal label. The HNTs with adequate hydroxyl groups are economically available raw materials. PPy, as an electrically conducting polymer material, can be absorbed to the surface of HNTs by in situ oxidative polymerization of the pyrrole monomer and form a shell on the HNTs. The shell of PPy could not only improve the conductivity of the nanocomposite but also absorb large amounts of Pd nanoparticles (NPs). The Pd NPs with high electrocatalytic activity toward the reduction of H2O2 and the HNTs@PPy-Pd nanocomposite as the analytical signal label could improve the sensitivity of the immunosensor. Under optimal conditions, the immunosensor showed a low detection limit (0.03 pg/mL) and a wide linear range (0.0001 to 25 ng/mL) of PSA. Moreover, its merits such as good selectivity, acceptable reproducibility, and stability indicate that the fabricated immunosensor has a promising application potential in clinical diagnosis. Graphical Abstract A new label-free amperometric electrochemical immunosensor based on HNTs@PPy-Pd nanocomposite for quantitative detection of PSA.


Asunto(s)
Silicatos de Aluminio/química , Técnicas Biosensibles/métodos , Nanotubos/química , Polímeros/química , Antígeno Prostático Específico/sangre , Pirroles/química , Anticuerpos Inmovilizados/química , Arcilla , Técnicas Electroquímicas/métodos , Humanos , Inmunoensayo/métodos , Límite de Detección , Masculino , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Nanocompuestos/química , Nanocompuestos/ultraestructura , Nanotubos/ultraestructura , Paladio/química
17.
Adv Skin Wound Care ; 30(4): 169-180, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28301357

RESUMEN

BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. RESULTS: In wild-type mice, topically applied MPH increased epithelial thickness. Levels of α-smooth muscle actin (α-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor ß levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas α-SMA and transforming growth factor ß levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased α-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. CONCLUSIONS: The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.


Asunto(s)
Cicatriz/tratamiento farmacológico , Hemostáticos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Materiales Biocompatibles , Modelos Animales de Enfermedad , Femenino , Hemostáticos/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Polisacáridos , Politetrafluoroetileno , Porosidad , Polvos
18.
Org Biomol Chem ; 14(26): 6225-30, 2016 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-27251032

RESUMEN

The first synthesis of a labdane-type diterpenoid isolated from Isodon yuennanensis was achieved in fourteen steps from commercially available starting material, (+)-sclareolide. The synthesis features the Barton nitrite ester reaction to introduce an oxime at the angular methyl group and the Jones oxidation to construct the lactone segment. By comparison of the optical rotation of our synthetic sample and the natural sample, the absolute stereochemistry of the natural diterpenoid has been determined.


Asunto(s)
Diterpenos/química , Diterpenos/síntesis química , Metacrilatos/química , Nitratos/química , Rizoma/química , Fluoruro de Sodio/química , Diterpenos/aislamiento & purificación , Conformación Molecular , Estereoisomerismo
19.
Nanomedicine ; 12(3): 623-632, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26656634

RESUMEN

Ultraviolet (UV) radiation has deleterious effects on living organisms, and functions as a tumor initiator and promoter. Multiple natural compounds, like quercetin, have been shown the protective effects on UV-induced damage. However, quercetin is extremely hydrophobic and limited by its poor percutaneous permeation and skin deposition. Here, we show that quercetin-loaded PLGA-TPGS nanoparticles could overcome low hydrophilicity of quercetin and improve its anti-UVB effect. Quercetin-loaded NPs can significantly block UVB irradiation induced COX-2 up-expression and NF-kB activation in Hacat cell line. Moreover, PLGA-TPGS NPs could efficiently get through epidermis and reach dermis. Treatment of mice with quercetin-loaded NPs also attenuates UVB irradiation-associated macroscopic and histopathological changes in mice skin. These results demonstrated that copolymer PLGA-TPGS could be used as drug nanocarriers against skin damage and disease. The findings provide an external use of PLGA-TPGS nanocarriers for application in the treatment of skin diseases. FROM THE CLINICAL EDITOR: Skin is the largest organ in the body and is subjected to ultraviolet (UV) radiation damage daily from the sun. Excessive exposure has been linked to the development of skin cancer. Hence, topically applied agents can play a major role in skin protection. In this article, the authors developed quercetin-loaded PLGA-TPGS nanoparticles and showed their anti-UVB effect.


Asunto(s)
Antioxidantes/uso terapéutico , Ácido Láctico/química , Ácido Poliglicólico/química , Quercetina/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Piel/efectos de los fármacos , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Vitamina E/química , Animales , Antioxidantes/administración & dosificación , Línea Celular , Portadores de Fármacos/química , Femenino , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Queratinocitos/efectos de la radiación , Ratones , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Quercetina/administración & dosificación , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/patología , Piel/patología , Enfermedades de la Piel/etiología , Enfermedades de la Piel/patología
20.
J Craniofac Surg ; 27(8): 1929-1933, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28005728

RESUMEN

Osteosarcoma of head and neck is a rare condition comprising of <1% of all head and neck cancers, retrospective studies show difference in survival of mandibular osteosarcoma to other head and neck sites, necessitating investigation into site-specific survival and recurrence rates.


Asunto(s)
Neoplasias Mandibulares/mortalidad , Recurrencia Local de Neoplasia/epidemiología , Osteosarcoma/mortalidad , Adulto , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Neoplasias Mandibulares/diagnóstico , Neoplasias Mandibulares/cirugía , Persona de Mediana Edad , Osteosarcoma/diagnóstico , Osteosarcoma/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias
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