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1.
Oncologist ; 25(11): e1725-e1731, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32627928

RESUMO

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is expected to improve local and systemic disease control and has been established as a standard therapy for several types of solid tumors. Considering the benefits of frontline radiation and pegaspargase in localized extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTL), we conducted a phase II study on pegaspargase-based CCRT to explore an effective treatment. MATERIALS AND METHODS: In this study, 30 patients with newly diagnosed nasal ENKTL in stages IE to IIE received CCRT (radiation 50 Gy and two cycles of pegaspargase 2,500 unit/m2 every 3 weeks). Four courses of pegaspargase were performed after CCRT. RESULTS: The patients completed CCRT and four cycles of pegaspargase. The complete remission (CR) rate was 90%, with a 95% confidential interval (CI) of 73.5%-97.9% after CCRT. The CR rate was 100% (95% CI, 88.4%-100%) at the end of the treatment. The 2-year overall survival and progression-free survival rates were 90.9% (95% CI, 78.4%-100%) and 92.8% (95% CI, 83.2%-100%), respectively. The major adverse events were in grades 1-2. CONCLUSION: Preliminary data indicate that pegaspargase combined with concurrent radiotherapy for newly diagnosed patients with nasal ENKTL was efficacious and well tolerated. Registered at www.chictr.org. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OIC-15007662. IMPLICATIONS FOR PRACTICE: This clinical trial, evaluating the efficacy and toxicity of concurrent chemoradiotherapy by using single-drug pegaspargase for patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) in stage IE to IIE, showed pegaspargase combined with concurrent radiotherapy was efficacious and well tolerated. Pegaspargase has a long half-life and is easy to administer via intramuscular injection. Consequently, pegaspargase combined with concurrent radiotherapy for patients with ENKTL can be completed in the outpatient clinic.


Assuntos
Asparaginase , Linfoma Extranodal de Células T-NK , Polietilenoglicóis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Quimiorradioterapia , Feminino , Humanos , Células Matadoras Naturais/patologia , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Linfoma Extranodal de Células T-NK/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Polietilenoglicóis/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
2.
Nat Chem Biol ; 14(1): 86-93, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29083418

RESUMO

Generating artificial pancreatic beta cells by using synthetic materials to mimic glucose-responsive insulin secretion in a robust manner holds promise for improving clinical outcomes in people with diabetes. Here, we describe the construction of artificial beta cells (AßCs) with a multicompartmental 'vesicles-in-vesicle' superstructure equipped with a glucose-metabolism system and membrane-fusion machinery. Through a sequential cascade of glucose uptake, enzymatic oxidation and proton efflux, the AßCs can effectively distinguish between high and normal glucose levels. Under hyperglycemic conditions, high glucose uptake and oxidation generate a low pH (<5.6), which then induces steric deshielding of peptides tethered to the insulin-loaded inner small liposomal vesicles. The peptides on the small vesicles then form coiled coils with the complementary peptides anchored on the inner surfaces of large vesicles, thus bringing the membranes of the inner and outer vesicles together and triggering their fusion and insulin 'exocytosis'.


Assuntos
Células Artificiais , Materiais Biomiméticos/química , Engenharia Celular/métodos , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Fusão de Membrana , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Concentração de Íons de Hidrogênio , Insulina/sangue , Secreção de Insulina , Masculino , Camundongos Endogâmicos C57BL
3.
J Sep Sci ; 43(11): 2172-2179, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130755

RESUMO

The present work reported a novel hydrophilic and selective solid-phase microextraction fiber by improved multiple co-polymerization method immobilization of tetracycline molecularly imprinted polymer on a stainless steel wire and directly coupled with high-performance liquid chromatography for sensitive determination of trace tetracyclines residues in animal derived foods. The developed molecularly imprinted polymer coated solid-phase microextraction fibers were characterized through scanning electron microscopy, Fourier transfer infrared spectroscopy, thermogravimetric analysis, and adsorption experiments, the fiber with cross-linked and porous structure was observed and high thermal and chemical stability. The maximum adsorption capacity of this fiber with good selectivity reached 2.35 µg/mg in aqueous matrices, and showed good repeatability (relative standard deviation ≤ 6.6%, n = 5) and satisfying reproducibility between fiber to fiber (relative standard deviation ≤ 7.8%, n = 5). Under the optimized solid-phase microextraction conditions, satisfactory linearity (5-1000 µg/L) and detection limits (0.38-0.72 µg/kg, S/N = 3) for all the tetracyclines were obtained. The practicality of this method was proved by adding tetracycline, oxytetracycline at three levels to milk, chicken, and fish samples with good recoveries of 77.3-104.4%.


Assuntos
Ração Animal/análise , Análise de Alimentos , Leite/química , Impressão Molecular , Microextração em Fase Sólida , Tetraciclinas/isolamento & purificação , Animais , Bovinos , Galinhas , Cromatografia Líquida de Alta Pressão , Peixes , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Polímeros/síntese química , Polímeros/química , Porosidade , Aço Inoxidável/química , Tetraciclinas/química
4.
J Sci Food Agric ; 100(10): 3822-3831, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32277468

RESUMO

BACKGROUND: Sulfonylureas are potentially toxic broad-spectrum herbicides. They pose a persistent threat to food safety and the environment. It is therefore important to develop a rapid and efficient pretreatment and detection method to prevent their harmful effects on human health. RESULTS: In the present work, a novel and highly selective absorbent for chlorosulfuron (CS) detection was prepared by the simple self-polymerization of dopamine on the surface of magnetic graphene oxide using a CS template. The resultant imprinted nanoparticles (MGO@PDA-MIPs) were characterized by transmission electron microscopy, X-ray diffraction, vibrating-sample magnetometry, thermogravimetric analysis, and nitrogen adsorption-desorption. The adsorption experiments demonstrated that the MGO@PDA-MIPs have excellent selectivity with regard to CS, with a high imprinting factor of 3.41 compared with a non-imprinted polymer. The nanoparticles rapidly achieve adsorption equilibrium and efficient desorption because there are numerous binding sites on the thin polydopamine imprinting layer. Under optimized conditions, the MGO@PDA-MIPs can be used to detect sulfonylurea residues in cereal samples by magnetic solid phase extraction coupled with high performance liquid chromatography (HPLC). The nanoparticles have a satisfactory recovery rate (80.65-101.01%) with a relative standard deviation (RSD) of less than 7.15%, and a limit of detection with regard to CS of 1.61 µg kg-1 (S/N = 3). They can also be re-used at least seven times. CONCLUSION: The MGO@PDA-MIPs have outstanding recognition performance, and can be prepared by a facile, single-step, and environmentally friendly process. They therefore have excellent potential for the recognition and separation of trace sulfonylurea herbicides in complex matrices. © 2020 Society of Chemical Industry.


Assuntos
Grão Comestível/química , Compostos Férricos/química , Grafite/química , Herbicidas/química , Indóis/química , Nanopartículas/química , Polímeros/química , Extração em Fase Sólida/métodos , Compostos de Sulfonilureia/química , Adsorção , Contaminação de Alimentos/análise , Herbicidas/isolamento & purificação , Polimerização , Extração em Fase Sólida/instrumentação , Compostos de Sulfonilureia/isolamento & purificação
5.
Mol Pharm ; 16(6): 2648-2660, 2019 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-31046290

RESUMO

The complement system plays an important role in host innate immunity, and its activation can be exploited as a potential strategy for vaccine adjuvants. Herein, a pH-responsive micellar vaccine platform (COOH-NPs) was developed using a carboxyl-modified diblock copolymer of poly(2-ethyl-2-oxazoline)-poly(d,l-lactide) (COOH-PEOz-PLA). The copolymer self-assembled into micelles with hydroxyl groups shielding on the surface, which activated the complement system for the enhanced immune responses. Compared with the control nanoparticles (OCH3-NPs), COOH-NPs significantly enhanced lymph node-resident dendritic cell maturation, antigen-specific IgG production, antigen-specific CD4+ and CD8+ T-cell activation, and the amount of memory T-cell generation in vivo. Furthermore, immunization with COOH-NPs/OVA in E.G7-OVA tumor-bearing mice not only remarkably inhibited tumor growth but also prolonged the survival of tumor-bearing mice. These results indicated that COOH-NPs with the capability of complement activation efficiently boosted the immune responses for the antitumor effect. The study demonstrated the significance of taking advantage of a complement-activating vaccine platform for cancer immunotherapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Polímeros/química , Animais , Células da Medula Óssea/metabolismo , Vacinas Anticâncer/imunologia , Ativação do Complemento/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Micelas , Nanopartículas/química
6.
Chem Soc Rev ; 47(8): 2518-2533, 2018 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-29557433

RESUMO

To date, liquid metals have been widely applied in many fields such as electronics, mechanical engineering and energy. In the last decade, with a better understanding of the physicochemical properties such as low viscosity, good fluidity, high thermal/electrical conductivity and good biocompatibility, gallium and gallium-based low-melting-point (near or below physiological temperature) alloys have attracted considerable attention in bio-related applications. This tutorial review introduces the common performances of liquid metals, highlights their featured properties, as well as summarizes various state-of-the-art bio-applications involving carriers for drug delivery, molecular imaging, cancer therapy and biomedical devices. Challenges for the clinical translation of liquid metals are also discussed.


Assuntos
Materiais Biocompatíveis/química , Metais/química , Animais , Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/toxicidade , Técnicas Biossensoriais/métodos , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Gálio/química , Humanos , Microfluídica/instrumentação , Microfluídica/métodos , Nanoestruturas/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico
7.
Acta Biomater ; 179: 325-339, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38561074

RESUMO

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.


Assuntos
Ferroptose , Lipossomos , Neurônios , Hemorragia Subaracnóidea , Ubiquinona , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Hemorragia Subaracnóidea/patologia , Animais , Ferroptose/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Lipossomos/química , Masculino , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL
8.
Angew Chem Int Ed Engl ; 52(29): 7451-4, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23765872

RESUMO

Better than expected: With a regular boronic acid as the functional monomer, a general and facile approach for glycoprotein imprinting exhibited several highly favorable features that are beyond normal expectation, which make the prepared MIPs feasible for the recognition of trace glycoproteins in complicated real samples.


Assuntos
Ácidos Borônicos/química , Glicoproteínas/química , Impressão Molecular , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Glicoproteínas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Polimerização , Polímeros/química , Polissacarídeos/química , Raios Ultravioleta
9.
Med ; 4(7): 404-431, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37244257

RESUMO

Solid organ transplant (SOT) recipients require meticulously tailored immunosuppressive regimens to minimize graft loss and mortality. Traditional approaches focus on inhibiting effector T cells, while the intricate and dynamic immune responses mediated by other components remain unsolved. Emerging advances in synthetic biology and material science have provided novel treatment modalities with increased diversity and precision to the transplantation community. This review investigates the active interface between these two fields, highlights how living and non-living structures can be engineered and integrated for immunomodulation, and discusses their potential application in addressing the challenges in SOT clinical practice.


Assuntos
Transplante de Órgãos , Transplantes , Materiais Biocompatíveis/uso terapêutico , Biologia Sintética , Imunossupressores/uso terapêutico
10.
J Control Release ; 360: 858-871, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37473808

RESUMO

Tumor-associated macrophages (TAMs) are the major immune cells infiltrating the tumor microenvironment (TME) and typically exhibit an immunosuppressive M2-like phenotype, which facilitates tumor growth and promotes resistance to immunotherapy. Additionally, tumor cells tend to express high levels of CD47, a "don't eat me" signal, that obstructs macrophage phagocytosis. Consequently, re-educating TAMs in combination with CD47 blockage is promising to trigger intense macrophage immune responses against tumors. As a toll-like receptor 7/8 agonist, resiquimod (R848) possesses the capacity to re-educate TAMs from M2 type to M1 type. We found that intratumoral administration of R848 synergistically improved the antitumor immunotherapeutic effect of CV1 protein (a SIRPα variant with high antagonism to CD47). However, the poor bioavailability and potential toxicity of this combo strategy remain a challenge. Here, a TAMs-targeted liposome (named: R-LS/M/CV1) co-delivering R848 and CV1 protein was constructed via decorating mannose on the liposomal surface. R-LS/M/CV1 exhibited high abilities of targeting, re-education and pro-phagocytosis of tumor cells to M2 macrophages in vitro. Intratumoral administration of R-LS/M/CV1 remarkedly eliminated tumor burden in the MC38 tumor model via repolarization of TAMs to M1 type, pro-phagocytosis of TAMs against tumors, and recruitment of tumor-infiltrating T cells. More encouragingly, due to the double targeting to TAMs and tumor cells of mannose and CV1 protein, R-LS/M/CV1 effectively accumulated at the tumor site, thereby not only remarkedly inhibiting tumors, but also exerting no hematological and histopathological toxicity when administered systemically. Our integrated strategy based on re-educating TAMs and CD47 blockade provides a promising approach to trigger macrophage immune responses against tumors for immunotherapy.


Assuntos
Lipossomos , Neoplasias , Humanos , Lipossomos/metabolismo , Antígeno CD47 , Manose , Macrófagos/metabolismo , Fagocitose , Neoplasias/metabolismo , Imunoterapia , Microambiente Tumoral
11.
Shanghai Kou Qiang Yi Xue ; 31(1): 104-108, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35587680

RESUMO

PURPOSE: This study was carried out to evaluate the value of comfort nursing in light curing resin-treated dental caries by means of patient satisfaction survey. METHODS: One hundred and twenty-eight cariogenic patients, who were treated from January 2017 to December 2017 in Shanghai Ninth People's Hospital, were enrolled and randomly assigned as experimental group and control group, respectively(n=64). Cariogenic lesions were treated with light-cured resin, patients in the control group received conventional four-handed operation nursing, while patients in the experimental group received modified comfortable nursing throughout the entire treatment course. The self-designed satisfaction questionnaires were issued, and the patients were required to fill them out after the treatment and nursing were definitely completed. The designed questionnaire was divided into two major parts, including nursing care and nursing operation, which was further subdivided into 10 detailed scoring items. The satisfaction survey of nursing was analyzed between two groups statistically to evaluate the effort of comfort nursing using SPSS 19.0 software package. RESULTS: No significant differences in the treatment environment was observed between the two groups(P>0.05), while upgraded satisfaction were observed in patients from the experimental group compared to those from the control group on the aspects of nursing care, namely, appearance, service attitude, explanation and health knowledge promotion(P<0.05). Among the five scoring standards of nursing operation, which was consist of timely initiative nursing, position nursing, eye nursing, effective nursing and nursing procedures, the satisfaction scores from the experimental group were significantly higher than those from the control group(P<0.05). The total collected data demonstrated that the overall satisfaction of the experimental group was significantly improved compared to that of the control group (94% vs 75%, P<0.01). CONCLUSIONS: Comfort nursing not only strengthens the professionalism of oral operation, but also improves the patient's experience, facilitating to promote the harmony between doctors and patients.


Assuntos
Cárie Dentária , China , Cárie Dentária/terapia , Suscetibilidade à Cárie Dentária , Humanos , Satisfação do Paciente
12.
J Pharm Sci ; 111(2): 450-457, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34547305

RESUMO

Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (ZEGFR) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR+ A431 tumor cells in vitro and in vivo. The LS-DDP coupled with ZEGFR (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro, AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 µg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 µg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of ZEGFR. In vivo, the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with ZEGFR enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR+ tumors.


Assuntos
Antineoplásicos , Cisplatino , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Receptores ErbB/metabolismo , Humanos , Lipossomos
13.
Curr Med Chem ; 26(8): 1377-1388, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-28933301

RESUMO

An emerging focus in nanomedicine is the exploration of multifunctional nanocomposite materials that integrate stimuli-responsive, therapeutic, and/or diagnostic functions. In this effort, cysteine-rich proteins have drawn considerable attention as a versatile platform due to their good biodegradability, biocompatibility, and ease of chemical modification. This review surveys cysteine-rich protein-based biomedical materials, including protein-metal nanohybrids, gold nanoparticle-protein agglomerates, protein-based nanoparticles, and hydrogels, with an emphasis on their preparation methods, especially those based on the cysteine residue-related reactions. Their applications in tumor-targeted drug delivery and diagnostics are highlighted.


Assuntos
Cisteína/química , Portadores de Fármacos/química , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Proteínas/química , Animais , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Ouro/química , Humanos , Hidrogéis/química , Nanocompostos/química , Nanopartículas/química , Nanotecnologia/métodos
14.
Sci Total Environ ; 670: 921-931, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30921724

RESUMO

The adsorbability on the carbonaceous cathode plays an important role in electro-Fenton systems but does not obtain enough attention. In this work, various carbon felts were obtained with different adsorption property by using the method of KOH activation at different temperatures to explore the influence of adsorption on the degradation efficiency of tetracycline (TC). The results of morphology characterization, nitrogen adsorption-desorption tests, XPS and FTIR analysis revealed that the surface area of carbon felt was improved, and the oxygen-containing functional groups on the surface were increased via KOH method with significantly enhanced adsorption capacity. In the batch experiment of TC electro-Fenton degradation, the carbon felt with better adsorption capacity tended to get higher degradation and mineralization efficiency. With the KOH activation process, CF-900 (carbon felt at 900 °C for 1 h) exhibited the best TC adsorption property for the removal of TC within 30 min (initial concentration: 80 mg/L). Meanwhile, the constant of reaction rate for TC degradation at the CF-900 is 0.0648 min-1. It is higher than that (0.012 min-1) obtained at the raw carbon felt (∼5 times of enhancement). There are also synergistic effects between adsorption and degradation performance on some other organic pollutants. In addition, the degradation pathway was also studied by the methods of solid-phase extraction and high performance liquid chromatography-mass spectrometry (HPLC). From the obtained results, it is shown that good adsorbability is favorable for degradation in the homogeneous electro-Fenton system.


Assuntos
Tetraciclina/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Adsorção , Carbono , Fibra de Carbono/química , Eletrodos , Tetraciclina/química , Poluentes Químicos da Água/química
15.
J Biomater Sci Polym Ed ; 29(4): 428-447, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29284363

RESUMO

Desired bone repair material must have excellent biocompatibility and high bioactivity. Moreover, mechanical properties of biomaterial should be equivalent to those of human bones. For developing an alternative biocomposite for load-bearing orthopedic application, combination of bioactive fillers with polymer matrix is a feasible approach. In this study, a series of multi-walled carbon nanotubes (MWCNTs)/poly(etheretherketone) (PEEK) bioactive nanocomposites were prepared by a novel coprecipitation-compounding and injection-molding process. Scanning electron microscope (SEM) images revealed that MWCNTs were adsorbed on the surface of PEEK particles during the coprecipitation-compounding process and dispersed homogeneously in the nanocomposite because the conjugated PEEK polymers stabilized MWCNTs by forming strong π-π stack interactions. The mechanical testing revealed that mechanical performance of PEEK was significantly improved by adding MWCNTs (2-8 wt%) and the experimental values obtained were close to or higher than that of human cortical bone. In addition, incorporation of MWCNTs into PEEK matrix also enhanced the roughness and hydrophilicity of the nanocomposite surface. In vitro cytocompatibility tests demonstrated that the MWCNTs/PEEK nanocomposite was in favor of cell adhesion and proliferation of MC3T3-E1 osteoblast cells, exhibiting excellent cytocompatibility and biocompatibility. Thus, this MWCNTs/PEEK nanocomposite may be used as a promising bone repair material in orthopedic implants application.


Assuntos
Cetonas/química , Nanocompostos/química , Nanotubos de Carbono/química , Polietilenoglicóis/química , Animais , Benzofenonas , Materiais Biocompatíveis , Adesão Celular , Linhagem Celular , Proliferação de Células , Humanos , Teste de Materiais , Camundongos , Osteoblastos/citologia , Polímeros , Próteses e Implantes , Propriedades de Superfície
16.
Int J Nanomedicine ; 13: 7135-7153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464464

RESUMO

BACKGROUND: Polyamidoamine (PAMAM) dendrimers modified by polyethylene glycol (PEG) have frequently been investigated as a delivery carrier for gene therapy. However, modification of PAMAM with PEG using covalent linkage significantly reduces the cellular uptake rate and the transfection efficiency. How to conquer these barriers becomes a burning question in gene delivery. MATERIALS AND METHODS: The present study constructed an effective disulfide bond-mediated cleavable RGD modified gene delivery system to overcome the aforementioned limitations. The disulfide bond was introduced between PAMAM dendrimers and PEG chains to realize the cleavage of PEG from the carrier system, whereas the arginine-glycine-aspartate (RGD) peptide was expected to promote the cellular uptake rate. A high mobility group Box 1 (HMGB1) protein containing nuclear localization signal (NLS) was simultaneously introduced to further promote gene expression efficiency. A pDNA/HMGB1/PAMAM-SS-PEG-RGD (DHP) nanocomplex was prepared via electrostatic interaction and characterized. RESULTS: The results showed that DHP generated small particles and was able to condense and protect pDNA against degradation. In addition, the RGD peptide could significantly promote the cellular uptake of a nanocomplex. Intracellular trafficking and in vitro expression study indicated that the DHP nanocomplex escaped from lysosomes and the disulfide bonds between PAMAM and PEG cleaved due to the high concentration of GSH in the cytoplasm, pDNA consequently became exclusively located in the nucleus under the guidance of HMGB1, thereby promoting the red fluorescence protein (RFP) expression. Importantly, an in vivo antitumor activity study demonstrated that the DHP nanocomplex had higher antitumor activity than any other reference preparation. CONCLUSION: All these results confirm that DHP could be a new strategy for improving the transfection and expression efficiency in gene delivery.


Assuntos
Dendrímeros/química , Dissulfetos/metabolismo , Proteína HMGB1/metabolismo , Sinais de Localização Nuclear/metabolismo , Oligopeptídeos/química , Transfecção , Células A549 , Animais , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , DNA/metabolismo , Dendrímeros/síntese química , Endocitose/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos , Nanopartículas/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Poliaminas/síntese química , Poliaminas/química , Polietilenoglicóis/química , Espectroscopia de Prótons por Ressonância Magnética , Eletricidade Estática
17.
Int J Nanomedicine ; 13: 6913-6927, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464450

RESUMO

BACKGROUND: Vectors are essential for successful gene delivery. In the present study, a tumor-targeting cationic gene vector, known as the disulfide cross-linked arginine-aspartic acid peptide modified by HAIYPRH (T7) peptide (CRD-PEG-T7), was designed for targeted delivery of plasmid DNA (pDNA) for gene therapy of prostate cancer (PCa). METHODS: The structure of CRD-PEG-T7 was determined and the cellular uptake efficacy, gene transfection efficacy, cytotoxicity, and the targeting effect of the CRD-PEG-T7-plasmid DNA complex were examined. RESULTS: The results demonstrated that the CRD-PEG-T7-plasmid DNA complex was nanosized and had a positively charged surface, good cellular uptake efficacy, minimal cytotoxicity, and a dual-targeting effect as compared with the CRD-PEG-plasmid DNA complex. The peptide T7-modifed new delivery system was able to target the highly expressed transferrin receptor (TfR) on tumor cells with an efficiency four-fold higher than that of the non-modified system. CONCLUSION: The results above indicatd that the CRD-PEG-T7-plasmid DNA complex may prove to be a promising gene delivery system targeting bone-metastatic tumor.


Assuntos
Colágeno Tipo IV/química , DNA/administração & dosagem , DNA/genética , Dissulfetos/química , Técnicas de Transferência de Genes , Terapia Genética , Fragmentos de Peptídeos/química , Plasmídeos/administração & dosagem , Neoplasias da Próstata/terapia , Animais , Benzoxazóis/química , Morte Celular , Linhagem Celular Tumoral , Movimento Celular , Colágeno Tipo IV/síntese química , Endocitose , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Fragmentos de Peptídeos/síntese química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Neoplasias da Próstata/patologia , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Quinolínio/química , Eletricidade Estática , Distribuição Tecidual , Transfecção , Transferrina/química
18.
ACS Appl Mater Interfaces ; 10(3): 3002-3010, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29292984

RESUMO

With the increasing demand for composites of multifunctional and integrated performance, graphene-based nanocomposites have been attracting increasing attention in biomedical applications because of their outstanding physicochemical properties and biocompatibility. High product yields and dispersion of graphene in the preparation process of graphene-based nanocomposites have long been a challenge. Further, the mechanical properties and biosafety of final nanocomposites are very important for real usage in biomedical applications. Here, we presented a novel high-throughput method of graphene on mechanical exfoliation in a natural honey medium, and a yield of ∼91% of graphene nanoflakes can be easily achieved with 97.76% of single-layer graphenes. The mechanically exfoliated graphene (MEG) can be well-dispersed in the poly(vinyl alcohol) (PVA) matrix. The PVA/MEG nanocomposite fibers are obtained by gel spinning and stretched 20 times. As a candidate for monofilament sutures, the PVA/MEG nanocomposite fibers with 0.3 wt % of MEG have an ultrahigh ultimate tensile strength of 2.1 GPa, which is far higher than that of the neat PVA fiber (0.75 GPa). In addition, the PVA/MEG nanocomposite fibers also have antibacterial property, low cytotoxicity, and other properties. On the basis of the above-mentioned properties, the effects of a common surgical suture and PVA/MEG nanocomposite fibers on wound healing are evaluated. As a result, the wounds treated with PVA/MEG nanocomposite fibers with 0.3 wt % of MEG show the best healing after 5 days of surgery. It is possible that this novel surgical suture will be available in the market relying on the gentle, inexpensive method of obtaining nonoxidized graphene and the simple process of obtaining nanocomposite fibers.


Assuntos
Nanocompostos , Antibacterianos , Grafite , Polímeros
19.
Chemosphere ; 209: 246-257, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29933161

RESUMO

The rapid, efficient and selective extraction of heavy metal ions is significant for wastewater pretreatment and metal ion recycle. Using montmorillonite as the template substrate and Pb2+ as template ions, a novel two-dimensional montmorillonite-based surface ion imprinted polymer (IIP-MMT) adsorbent is successfully synthesized via activators generated by electron transfer for atom transfer radical polymerization (AGET-ATRP). Batch adsorption experiments are performed to assess the properties of the imprinted polymer sorbent, along with its selectivity and reusability in practical extraction of Pb2+. It is interesting that the crosslinking density of the imprinted polymer has impact on the sorption property, where suitable density is coupled with the highest adsorption capacity and the best selectivity. Benefiting from the surface-imprinting technique and AGET-ATRP, IIP2-MMT is proved to own a highly effective Pb2+ adsorption capacity to reach 158.68 mg/g within 30 min, where the corresponding maximum adsorption capacity is 201.84 mg/g. Moreover, this material exhibits satisfactory stability and reusability that the high adsorptive capability of IIP-MMT retains more than 95% after six cycles. Thus, it is expected to reduce the wastewater disposal expenses. Besides, owing to the characteristics of PHEMA brushes and SHA chelating ligand, IIP-MMT has strong anti-interference and anti-blockage abilities to extract Pb2+ from smelting wastewater, slag and contaminated soil. Considering the low cost, excellent stability, high extraction efficiency, environmental friendliness, it is expected that the proposed material is very promising for treatment of heavy metals-contaminated wastewaters and soil, or ion recycle.


Assuntos
Bentonita/química , Chumbo/isolamento & purificação , Impressão Molecular/métodos , Polímeros/química , Águas Residuárias/química , Adsorção , Íons , Metais Pesados/isolamento & purificação , Poluentes do Solo/isolamento & purificação
20.
ACS Nano ; 11(1): 613-620, 2017 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-28051306

RESUMO

A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Glucose/metabolismo , Peróxido de Hidrogênio/química , Hipoglicemia/tratamento farmacológico , Insulina/administração & dosagem , Adesivo Transdérmico , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Glucose/análise , Glucose Oxidase/metabolismo , Insulina/química , Insulina/farmacologia , Cinética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Polímeros/síntese química , Polímeros/química , Estreptozocina
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