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1.
Am J Emerg Med ; 38(10): 2101-2109, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33184025

RESUMO

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.


Assuntos
COVID-19/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Índice de Gravidade de Doença , China/epidemiologia , Estado Terminal/epidemiologia , Estudos Transversais , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
2.
Artigo em Inglês | MEDLINE | ID: mdl-25196448

RESUMO

A supramolecular block copolymer is prepared by the molecular recognition of nucleobases between poly(2-(2-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)-SS-poly(ε-caprolactone)-adenine (P(MEO2 MA-co-OEGMA)-SS-PCL-A) and uracil-terminated poly(ethylene glycol) (PEG-U). Because the block copolymer is linked by the combination of covalent (disulfide bond) and noncovalent (AU) bonds, it not only has similar properties to conventional covalently linked block copolymers but also possesses a dynamic and tunable nature. The copolymer can self-assemble into micelles with a PCL core and P(MEO2 MA-co-OEGMA)/PEG shell. The size and morphologies of the micelles/aggregates can be adjusted by altering the temperature, pH, salt concentration, or adding dithiothreitol (DTT) to the solution. The controlled release of Nile red is achieved at different environmental conditions.

3.
Int J Biol Macromol ; 262(Pt 2): 129996, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342271

RESUMO

The limitations of traditional therapeutic methods such as chemotherapy serious restricted the application in tumor treatment, including poor targeting, toxic side effects and poor precision. It is important to develop non-chemotherapeutic systems to achieve precise and efficient tumor treatment. Therefore, a functional metal-organic framework material (MOF) with porphyrin core and doped with Cu2+ and surface-modified with polydopamine (PDA), namely PCN-224(Cu)@PDA (PCP) was designed and prepared. After loaded into the injectable and self-healable hydrogels by dynamic Schiff base bonding of oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMC), the multifunctional nanocomposite hydrogels were obtained, in which Cu2+ in MOF converts to Cu+ by reacting with glutathione (GSH) which reduces the tumor antioxidant activity to improve the CDT effect. The Cu2+/Cu+ induces Fenton-like reaction in tumor cells to produce a toxic hydroxyl radical (OH). PDA achieves photothermal conversion under NIR light for photothermal therapy (PTT), and porphyrin core as a ligand generates reactive oxygen species (ROS), presenting highly efficient photodynamic therapy (PDT). Injectable self-healing hydrogel as a loading platform can be in situ injected to tumor site to release PCP and endocytosed by tumor cells to achieve precise and synergistic CDT-PDT-PTT therapy.


Assuntos
Quitosana , Nanopartículas , Neoplasias , Porfirinas , Humanos , Nanogéis , Alginatos , Glutationa , Hidrogéis , Óxidos , Linhagem Celular Tumoral , Peróxido de Hidrogênio
4.
Int J Biol Macromol ; 253(Pt 1): 126625, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37657577

RESUMO

Diabetic severe wound healing is challenging and also carries a high risk of bacterial infection and may be accompanied by serious complications. Electrical stimulation (ES) can effectively promote wound healing, but its effectiveness is often limited by incomplete contact between the electrodes and the wound site. In order to improve the efficiency of electrical stimulation utilization and to avoid wound infection, a multi-dynamically crosslinked nanocomposite hydrogel was prepared from dextran modified with aldehyde groups and phenylboronic acid esters (Dex-FA-BA), carboxymethyl chitosan (CMCS), polyaniline grafted chitosan oligosaccharide (CP), and Epigallocatechin Gallate/Ca2+ modified melanin-like nanoparticles (CEMNPs), based on dynamic Schiff base bonds, phenylboronic acid/diol interactions, and hydrogen bonding. The CEMNPs have good photothermal conversion properties and antioxidant activity and can also enhance the mechanical properties of the hydrogel system. The CP endows the hydrogel with good electrical conductivity and sensing properties and can record the respiratory and heart rate of rats in real time. Based on the convolutional neural networks (CNN) algorithm constructed by ResNet9, the respiratory and heart rate signals can be distinguished with 93.9 % accuracy. This multifunctional nanocomposite hydrogel can provide a new strategy to promote chronic wound healing and achieve health monitoring effectively.


Assuntos
Quitosana , Diabetes Mellitus , Animais , Ratos , Nanogéis , Dextranos , Frequência Cardíaca , Antibacterianos , Condutividade Elétrica , Hidrogéis , Oligossacarídeos
5.
J Mater Chem B ; 11(16): 3727-3739, 2023 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-37067286

RESUMO

Efficient synergistic therapeutic strategies for tumors with high specificity and sensitivity remain a major challenge. An injectable near-infrared (NIR)-responsive supramolecular hydrogel was prepared via host-guest interactions between conjugated poly(N-phenylglycine)-poly(ethylene glycol) (PNPG-PEG) and α-cyclodextrin. A reactive oxygen species (ROS)-triggered chain-breakage prodrug was composed of a thioketal (TK) linkage of methoxy poly(ethylene glycol) (mPEG) and doxorubicin (DOX). The resulting amphiphilic conjugate mPEG-TK-DOX can self-assemble into prodrug micelles. PEG/poly(etherimide) (PEI)@Fe3O4 nanoparticles (PEG/PEI@Fe3O4 NPs) were prepared using a thermal decomposition method. The prodrug micelles and PEG/PEI@Fe3O4 NPs can be well dispersed into the hydrogel system. In a tumor micro-acid environment, PEG/PEI@Fe3O4 NPs catalyze the decomposition of H2O2 to highly toxic ˙OH via a Fenton reaction to induce the breakage of ROS-responsive TK bonds for the dissociation of micelles and the continuous release of DOX. PEG/PEI@Fe3O4 NPs can also generate an NIR-thermal effect and enhance the photothermal therapy. Notably, by combining with controllable photothermal therapy, the in situ composite hydrogel system shows enhanced synergistic chemo-photothermal therapy for tumors and almost complete in vitro and in vivo tumor suppression, providing a promising synergistic tumor treatment strategy.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Doxorrubicina/química , Hidrogéis/química , Peróxido de Hidrogênio , Micelas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Polietilenoglicóis/química , Pró-Fármacos/farmacologia , Espécies Reativas de Oxigênio
6.
J Mater Chem B ; 11(45): 10883-10895, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37917009

RESUMO

Traditional cancer therapies no longer meet the current demand for cancer precision therapy and personalized treatment and it's essential to develop new therapeutic modalities as well as to investigate new combination anti-tumor mechanisms. Therefore, amphiphilic prodrug polymer chains linking methoxy poly(ethylene glycol) (mPEG) and cinnamaldehyde (CA) with adipic acid dihydrazide (ADH) as the pH-responsive center were designed and synthesized, which could self-assemble into PAC micelles in aqueous solution. A supramolecular hydrogel was formed based on the host-guest interaction between α-cyclodextrin (α-CD) and PAC micelles. Polyetherimide (PEI) modified copper manganese sulfide nanoenzyme catalysts (PCMS NPs) were prepared by a solvothermal method, which could be uniformly dispersed in the hydrogel to form a composite supramolecular hydrogel (PCMS@PAC/α-CD Gel). Under an acidic tumor environment, pH-responsive hydrazone bonds were broken, resulting in the slow release of CA and the amplification of hydrogen peroxide (H2O2) levels. PCMS NPs exerted peroxidase (POD)-like activity and catalase (CAT)-like activity, which could convert H2O2 into hydroxyl radicals (˙OH) and oxygen (O2) to alleviate intra-tumor hypoxia and induce apoptosis, while exerting glutathione oxidase (GPX)-like activity to consume glutathione (GSH) to further enhance the effect of chemodynamic therapy (CDT). Under near-infrared light (NIR) irradiation, PCMS NPs exhibited an excellent photothermal conversion performance, which could rapidly increase the temperature of tumor cells to above 42 °C for photothermal therapy (PTT) and convert O2 to a superoxide anion (˙O2-) by exerting oxidase (OXD)-like activity for photodynamic therapy (PDT). It was demonstrated by in vitro and in vivo experiments that the PCMS@PAC/α-CD Gel was highly cytotoxic to cancer cells and could effectively inhibit tumor growth, indicating the potential for applications in the fields of biomedicine and smart materials.


Assuntos
Hidrogéis , Neoplasias , Humanos , Hidrogéis/farmacologia , Peróxido de Hidrogênio , Micelas , Terapia Fototérmica , Concentração de Íons de Hidrogênio
7.
Carbohydr Polym ; 310: 120721, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36925247

RESUMO

Nowadays, the photothermal therapy (PTT) has received widespread attention and research by rapidly killing tumors with local high temperature. However, due to the irregular edges of tumor and the blurred boundary between normal and necrotic tissues, the desirable treatment cannot be achieved by the single PTT, and excessive heat will cause serious inflammation in local tissues. Herein, an injectable composite hydrogel is prepared by the oxidized hyaluronic acid (OHA) and hydroxypropyl chitosan (HPCS) via the imine bonds, which is employed as the delivery substrate for functional substances. In the gel medium, the mesoporous polydopamine (MPDA) nanoparticles are incorporated as the high efficiency photothermal agent and a reservoir of DOX, which can achieve the good photothermal conversion performance and pulsed drug release. Besides, the addition of the curcumin-cyclodextrin host-guest inclusion complex (CUR@NH2-CD) in the composite hydrogel could reduce the inflammation caused by PTT. The composite hydrogel shows favorable the Hepa1-6 tumor inhibition in vivo by virtue of the comprehensive effect of the admired photothermal efficacy of MPDA, chemotherapy of DOX and anti-inflammatory of CUR. It can be predicted that the composite hydrogel has a broad prospect in the field of comprehensive therapy for tumor.


Assuntos
Quitosana , Nanopartículas , Neoplasias , Humanos , Quitosana/uso terapêutico , Terapia Fototérmica , Ácido Hialurônico/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Nanogéis/uso terapêutico , Fototerapia/métodos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/química , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Hidrogéis/química
8.
Nanotechnology ; 23(50): 505706, 2012 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-23183247

RESUMO

The magnetocaloric effects and lower critical solution temperature (LCST) were investigated in a magnetothermally-responsive nanocarrier for magnetothermal drug release under alternating magnetic field (AMF). The Mn(0.2)Zn(0.8)Fe(2)O(4) nanoparticles with low T(c) were dispersed in a polymeric matrix consisting of N-Isopropyl acrylamide (NIPAAm) and N-hydroxymethyl acrylamide (HMAAm). The magnetocaloric effects and LCST of the nanocarriers were characterized by using high-resolution electron transmission microscopy, thermogravimetric analyses, and vibrating sample magnetometer. The maximum self-heating temperature of 42.9 °C was achieved by optimizing the Mn(0.2)Zn(0.8)Fe(2)O(4) concentration in the polymer matrix. By adjusting the NIPAAm to HMAAm ratio, the LCST was controlled at an ideal level of 40.1 °C for efficient thermosensitive drug delivery. Magnetothermally responsive drug release of Doxorubicin, an anticancer drug, was significantly enhanced by application of an external AMF on the nanocarriers. The cytotoxicity experimental results in vitro show good biocompatibility and efficient therapeutic effects in cancer treatment.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/química , Doxorrubicina/administração & dosagem , Nanopartículas/química , Acrilamidas/química , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Humanos , Ferro/química , Campos Magnéticos , Manganês/química , Nanopartículas/ultraestrutura , Neoplasias/tratamento farmacológico , Temperatura , Zinco/química
9.
ACS Appl Mater Interfaces ; 14(25): 29273-29283, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35704849

RESUMO

In recent years, gel-based sensors have been widely considered and fully developed. However, it is of vital importance, yet rather challenging to achieve a multifaceted gel, which can unify the advantages of favorable conductivity, high adhesion, excellent environmental resistance, and so forth and be applied in various harsh conditions. Herein, an ideal, extremely stable, adhesive, conductive poly(ionic liquid) gel (PILG) was designed via a one-step photoinitiated radical polymerization based on 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide (VBIm-NTf2) cross-linked with ethylene glycol dimethacrylate (EGDMA) in methyltributylammonium bis(trifluoromethanesulfonyl)imide (N1444-NTf2) medium. There are abundant hydrophobic butyl chains and fluorinated groups in VBIm-NTf2 and N1444-NTf2, which can impart the PILG with stable conductivity, excellent environmental tolerance, and adhesion even in water due to the ion-dipole and ion-ion interactions. The resulting PILG can be assembled as a soft and smart sensor that can be applied in specific conditions such as underwater or undersea and even in dynamic water, achieving a stable signal transmission. Meanwhile, the PILG can be utilized as a flexible electrode to convey ECG signals in air or water whether it is in the static or dynamic state. Therefore, it is envisioned that this novel PILG will serve as a hopeful electrical device for signal detection and healthy management in specific environments.

10.
ACS Appl Mater Interfaces ; 14(33): 38205-38215, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-35952384

RESUMO

Conductive hydrogels as flexible wearable devices have attracted considerable attention due to their mechanical flexibility and intelligent sensing. How to endow more and better performance, such as high self-adhesion, stretchability, and wide application temperature range for traditional hydrogels and flexible sensors is a challenge. Herein, a stretchable, self-adhesive, and antifreezing conductive hydrogel with multiple networks and excellent mechanical properties was prepared by a two-step method for its application in sensitive motion sensors and temperature-/humidity-driven actuators. First, quaternary chitosan (QCS) was introduced into the network of an acrylamide (AM) and 1-vinyl imidazole (VI) copolymer initiated by UV-photoinitiated radical polymerization. Then, the double-network hydrogel was immersed in a FeCl3 solution to fabricate the P(AAm-co-VI)/QCS-Fe3+ ionic hydrogel with multiple physical networks. The properties of the hydrogel were controllable and adjustable. The toughness of the ionic hydrogel could reach up to 654.4 kJ/m3, the fracture strength could reach 253.1 kPa, and the compressive strength reached 8.4 MPa at an 80% compression strain. The multiple physical networks improved the mechanical properties and the quick resilience of the hydrogel. A large amount of FeCl3 in the network greatly enhanced the ionic conductivity. Meanwhile, hydrogen bonds with water molecules inhibit the formation of ice crystals between zero water molecules and enhance the freezing resistance of P(Aam-co-VI)/QCS hydrogels. The active group on the QCS chain provided adhesiveness to various substrates for hydrogels. The P(AAm-co-VI)/QCS-Fe3+ hydrogel-based sensor showed high sensitivity, which can detect human movement and pulse, with a gauge factor of 2.37. Finally, due to the different dehydration rates of the P(AAm-co-VI)/QCS-Fe3+ and P(AAm-co-VI)/QCS hydrogel, a double-layer temperature/humidity-driven actuator was fabricated, expanding the application of conductive hydrogels.

11.
Macromol Biosci ; 22(9): e2200161, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35676757

RESUMO

In order to overcome the limitation of traditional therapies for cancer and improve the accuracy of treatment, more advantageous cancer treatment methods need to be explored and studied. As a result, photothermal photodynamic therapy of breast cancer using bovine serum albumin (BSA) modifies molybdenum disulfide nanoflakes. Then the well-dispersed BSA-MoS2 NFs are loaded in the injectable and self-healing polysaccharide hydrogel which is prepared by the reaction of oxidized sodium alginate (OSA) and hydroxypropyl chitosan (HPCS) through the formation of Schiff base bonds. The injection and self-healing properties of the nanocomposite hydrogel are investigated. In vitro photothermal and photodynamic investigations demonstrate that BSA-MoS2 NFs possess obvious photothermal conversion and production of reactive oxygen species (ROS) under the irradiation of near infrared (NIR) laser (808 nm). In vivo anticancer investigation indicates that the nanocomposite hydrogel can be directly injected and remain in the tumor sites and achieve the synergistic photothermal-photodynamic therapy of cancer.


Assuntos
Neoplasias , Fotoquimioterapia , Dissulfetos , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Molibdênio/química , Molibdênio/farmacologia , Nanogéis , Fototerapia/métodos , Polissacarídeos/farmacologia , Soroalbumina Bovina/química
12.
ACS Appl Mater Interfaces ; 14(49): 55075-55087, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36455289

RESUMO

Nowadays, with the rapid development of artificial intelligence, conductive hydrogel-based sensors play an increasingly vital role in health monitoring and temperature sensing. However, the perfect integration of the environmental stability and applied performance of the hydrogel has always been a challenging and significant problem. Herein, we report an environmentally tolerant, stretchable, adhesive, self-healing conductive gel through multiple dynamic interactions in the water/glycerol/ionic liquids medium, which can be used as a high-performance strain and temperature sensor. The random copolymer poly(acrylic acid-co-acetoacetoxyethyl methacrylate) interacts with the branched poly(ethylene imine) (PEI) and Zr4+ ions via the dynamic covalent enamine bonds, coordinations, and electrostatic interactions to improve stretchable (1300%), compressible, fatigue-resistant (1000 cycles at 50% strain), and self-healing performance (95%, 24 h). The combination of water/glycerol/ionic liquids imparts the resulting gel with excellent electrical conductivity, anti-drying, and anti-freezing performance. By means of the above excellent performance, the gel could be used as the flexible strain or pressure sensor with high sensitivity and stability for the detection of the movement, expression, handwriting, pronouncing, and electrocardiogram (ECG) signals in various models. Meanwhile, the resulting gel can be assembled as the temperature sensor to trace the change of temperature accurately and steadily, which has a wide operating window (0 to 100 °C), an ultralow detection limit (0.2 °C), and high sensitivity (2.1% °C-1). It is believed that the strategy for the multifunction and high-performance gel will blaze a new trail for the smart device in health management, temperature detection, and information transmission under various environmental conditions.

13.
ACS Appl Mater Interfaces ; 13(3): 4508-4518, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33439012

RESUMO

Flexible and intelligent electronics are highly demanded in wearable devices and systems, but it is still challenging to fabricate conductive textiles with good stretchability, multifunctionality, and responsiveness to multistimuli. Therefore, kinds of smart conductive fabrics with high stretchability and thermal properties, good washability, excellent shape stability, rapid responsiveness to external stimuli (e.g., electrical and photonic), and outstanding energy conversion and storage properties were designed and prepared. The nonwoven smart fabrics were fabricated by electrospinning of a solution of multiwalled carbon nanotubes (MWCNTs)/lauric acid (LA)/thermoplastic polyurethane (PU) and dip-coating conductive polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) on the obtained nanofibers. The smart textiles showed tunable temperature and phase change enthalpy that responded to external stimuli such as electrical voltage, infrared light, and sunlight. At the same time, they realized the storage and conversion of energy reversibly with a high efficiency. The elastic fabrics could also be used as a stretchable conductor in a range of deformation. The integrative functions of the smart fabrics promise them great potential in wearable systems and intelligent protective garments.

14.
ACS Appl Mater Interfaces ; 13(1): 1474-1485, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33393770

RESUMO

As a flexible wearable device, hydrogel-based sensors have attracted widespread attention in soft electronics. However, the application of traditional hydrogels at extreme temperatures or for a long-term stability still remain a challenge because of the existence of water. Herein, we reported an antifreezing and antidrying organohydrogel with high transparency (over 85% transmittance), high stretchability (up to 1200%), and robust adhesiveness to various substrates, which consist of polyacrylic acid, gelatin, AlCl3+, and tannic acid in a water/glycerin binary solvent as the dispersion medium. As the binary solvent easily forms strong hydrogen bonds with water molecules, organohydrogels exhibited excellent tolerance for drying and freezing. The organohydrogels maintained conductivity, adhesion, and stable sensitivity after a long-term storage or at subzero temperature (-14 °C). Moreover, the organohydrogel-based wearable sensors with a gauge factor of 2.5 (strain, 0-100%) could detect both large-scale movements and subtle motions. Therefore, the multifunctional organohydrogel-wearable sensors with antifreezing and antidrying properties have promising potential for human-machine interfaces and healthcare monitoring under a broad range of environmental conditions.

15.
ACS Appl Mater Interfaces ; 13(44): 53055-53066, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34699172

RESUMO

The demand for wearable sensors consisting of multifunctional conductive hydrogels with fatigue resistance and adhesion properties is rising. More importantly, it is necessary to improve the freezing tolerance and dehydration resistance of hydrogels to avoid performance degradation in harsh environments. Herein, a robust nanocomposite ionogel was fabricated in [EMIM][Cl] ionic liquid and clay nanosheets were used as physical cross-linkers through rapid UV polymerization. The excellent mechanical properties, repeated self-adhesion to various substrates, freezing tolerance, and anti-drying properties were integrated into the nanocomposite ionic liquid hydrogel. The addition of clay nanosheets Laponite XLG endowed the ionogel with a high stretchability of up to 1200% and a tensile strength of up to 0.14 MPa, and the ionogel could be recovered when the external force was released. Ascribing to ionic liquids, the nanocomposite ionogel displayed ionic conductivity and temperature tolerance. An ionogel battery with a 0.72 V output voltage was formed by assembling the ionogel with a layer of zinc and copper sheet on each side to realize the conversion from chemical energy to electrical energy. The maximum voltage could reach 2.8 V when the four units are combined, which could provide energy for an LED bulb and could be used as a self-powered strain sensor under harsh conditions. In this work, a multifunctional ionogel self-powered sensor is proposed, which has potential applications in the fields of electronic skin, human-machine interaction, and biosensors over a wide temperature range.

16.
J Mater Chem B ; 9(47): 9734-9743, 2021 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-34787633

RESUMO

Non-chemotherapeutic tumour treatment has received extensive attention due to its having fewer side effects as compared to chemotherapy. However, nanomaterials-based non-chemotherapy still faces limitations such as poor targeting and low retention. Therefore, a Schiff base cross-linked hydrogel was designed and prepared using aldehyde-modified polyethylene glycol (PEG) and carboxymethyl chitosan (CMC). This hydrogel has good injectable and self-healing properties and can carry graphene oxide (GO) as a photothermal agent and needle-like nano-hydroxyapatite (HAP) as a tumour inhibitor. Combined with tumour proliferation inhibition therapy and photothermal therapy, the nanocomposite hydrogel system can avoid the side effects of chemotherapy and improve the accuracy of tumour treatment. The PEG-CMC/HAP/GO nanocomposite hydrogel system has a porous structure, good injectability and self-healing properties to meet the mechanical requirements. In vitro cell characterization showed that GO is phototoxic to tumour cells, HAP can inhibit the proliferation of tumour cells, the nanocomposite hydrogel remained in the tumour site, and the encapsulated GO and HAP did not transfer to the normal site and cause cell damage. In the in vivo investigation, the breast cancer tumour-bearing mice, the model animals for tumour treatment, were treated with an intratumoral injection of the PEG-CMC/HAP/GO nanocomposite hydrogel. This functional self-healing hydrogel loaded with GO and HAP effectively inhibited tumour cell proliferation and realized the synergistic effect of photothermal therapy, which is expected to become a new effective treatment approach for tumours.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Durapatita/uso terapêutico , Grafite/uso terapêutico , Hidrogéis/química , Nanocompostos/química , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quitosana/análogos & derivados , Quitosana/química , Grafite/efeitos da radiação , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Terapia Fototérmica , Polietilenoglicóis/química
17.
Biomater Sci ; 8(12): 3348-3358, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32458834

RESUMO

Hypoxia is an important pathological phenomenon due to uncontrolled cancer cell proliferation and insufficient blood flow, which can be used to design hypoxia-responsive nanocarriers for the intelligent treatment of tumor. However, it is difficult to obtain the response of hypoxia-responsive polymers corresponding to the degree of hypoxia in the tumor sites. Therefore, hypoxia-responsive azobenzene-centered copolymers polyoligo (ethylene glycol) methacrylate-block-poly(ε-caprolactone)-azobenzene-poly(ε-caprolactone)-block-poly oligo (ethylene glycol) (POEGMA-b-PCL-Azo-PCL-b-POEGMA) were synthesized and further self-assembled into spherical micelles. Doxorubicin (DOX) and chlorine e6 (Ce6) were encapsulated inside the micelles. The photodynamic therapy (PDT) of Ce6 could be applied to further amplify the hypoxia condition in the tumor sites through oxygen consumption on laser irradiation (660 nm). Under this condition, the DOX/Ce6-loaded micelles progressively formed spherical micelles with a small size due to the cleavage of azobenzene, thus allowing the controlled release of DOX. The formed smaller micelles could significantly avoid the formation of large aggregates, which is beneficial for clinical application. Moreover, Ce6 would continuously convert oxygen to singlet oxygen (1O2), thus showing toxicity to cancer cells. Both in vitro and intracellular studies confirmed that our "all-in-one" micelles showed a superior synergistic effect of photodynamic therapy and chemotherapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Compostos Azo/administração & dosagem , Doxorrubicina/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Porfirinas/administração & dosagem , Animais , Antibióticos Antineoplásicos/química , Compostos Azo/química , Hipóxia Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Clorofilídeos , Doxorrubicina/química , Luz , Camundongos , Micelas , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/administração & dosagem , Polímeros/química , Porfirinas/química , Porfirinas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
18.
ACS Appl Mater Interfaces ; 12(8): 9118-9131, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32009384

RESUMO

Injectable and self-healing hydrogels with thermoresponsiveness as smart hydrogels displayed injectability, automatic healing, and phase and volume changes as well. Here, the thermoresponsive self-healing hydrogel was prepared via the formation of dynamic covalent enamine bonds between the amino groups in polyetherimide (PEI) and the acetoacetate groups in the four-armed star-shaped poly(2-(dimethylamino)ethyl methacrylate-co-2-hydroxyethyl methacrylate) modified with tert-butyl acetoacetate (t-BAA), SP(DMAEMA-co-HEMA-AA). After adding polydopamine nanoparticles (PDA NPs), the SP(DMAEMA-co-HEMA-AA)/PEI/PDA-NP nanocomposite hydrogel presented phase change and volume shrinkage under near-infrared (NIR) irradiation. The thermoresponsive nanocomposite hydrogel loaded with the anticancer drug doxorubicin (DOX) could be injected into the 4T1 tumor by intratumoral injection. After NIR laser irradiation, the temperature of the hydrogel increased because of the photothermal effect of PDA NPs inducing local hyperthermia. Because the hydrophilicity-hydrophobicity transition of the hydrogel occurred, DOX molecules were squeezed out from the hydrogel at temperatures higher than its lower critical solution temperature (LCST) and the tumor cells suffered from internal stress from the shrunk hydrogel. The injectable nanocomposite hydrogel not only demonstrated the synergism of highly efficient thermochemotherapy but also showed the function of improving drug utilization and precise treatment to reduce the side effects of drugs.


Assuntos
Doxorrubicina , Hidrogéis , Hipertermia Induzida , Indóis , Nanopartículas , Neoplasias Experimentais/terapia , Polímeros , Animais , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Indóis/química , Indóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Polímeros/química , Polímeros/farmacologia
19.
Cancer Med ; 9(24): 9632-9640, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33128354

RESUMO

Pancreatic cancer (PC) is one of the most malignant gastrointestinal tumors and the 5-year survival is only 9%. The expression of miRNAs in serum has been proved to be related to tumorigenesis and development of cancers. The miRNA targets and gene targets were predicted in microRNA.org, miRDB, TargetScan, and RNAInter. The expression data of STK31 (Serine/Threonine Kinase 31) and miRNAs generated from PC samples was from TCGA and the relationship of expression of STK31 and miR-543 was confirmed in PC samples from our center. Double luciferase reporter gene assay was used to demonstrate the direct binding between miR-543 and STK31. The effect of expression level of miRNAs on survival time was assessed by Kaplan-Meier curves. The Go Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miR-543-related genes were performed. The results showed that miR-543 had a statistically significant correlation with the expression of STK31 and contained the direct binding site with STK31. The expression level of miR-543 may affect the survival of PC. The results of GO and KEGG pathway analysis showed that miR-543 might play a key role in Insulin signaling pathway. MiR-543 could be combined with STK31 and affect the expression of STK31. The expression of miR-543 could also predict the survival of patients with PC, which suggested that miR-543 might play an important role in PC. The GO and KEGG pathway analysis also displayed that miR-543 was involved in several other pathways of pancreas.


Assuntos
Biologia Computacional/métodos , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Bases de Dados Genéticas , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Taxa de Sobrevida
20.
ACS Appl Mater Interfaces ; 11(43): 40620-40628, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31595740

RESUMO

The artificial skin-like stretchable ionic sensor device usually requires a synergistic effect of reliable adhesion between human machine interface, reasonable mechanical strength, and visually displayable transparency. A plant-inspired zwitterionic hydrogel was prepared through rapid UV initiation in the existence of cellulose nanocrystals as physically crosslinker and reinforcing agent. The resulting transparent zwitterionic nanocomposite hydrogel successfully brings the synergistic advantages of robust adhesive strength between diversified substrates such as skins, plastics, glass, and steels with remarkable mechanical properties of a superior stretchability over 1000% strain, a mechanical tensile strength up to 0.61 MPa, and compressive strength up to 7.5 MPa, manifesting in superior ionic transport performance, simultaneously. Furthermore, the zwitterionic nanocomposite hydrogel was fabricated as a wearable compliant stretchable pressure-strain sensor in the modality of the skin-adhesive patch to be sensitive to human motion such as finger touch and speech recognition for personal healthcare of patient sensory rebuilding and physiological data acquisition. It maintains compressive cycling sensibility at diverse pressure during 0.5, 1.0, and 1.5 Hz, respectively. The multifunctional zwitterionic nanocomposite hydrogel could also be assembled into flexible electrical devices such as luminescent display and information transfer between human and robot communication for mechanosensory electronics and artificial intelligence.


Assuntos
Adesivos/química , Materiais Biomiméticos/química , Hidrogéis/química , Nanocompostos/química , Pele Artificial , Estresse Mecânico , Humanos
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