RESUMO
Mitochondrial sulfur dioxide (SO2) and formaldehyde (FA) in cancer cells serve as important signal molecules in mediating multiple physiological and pathological activities. Accurate monitoring of the dynamic fluctuation of SO2 and FA in the mitochondria of cancer cells is important for insight into their relationships and functions in cancer, understanding cancer mechanism, and the role of mitochondrial homeostasis in cancer invasion and metastasis. Herein, a novel integrated two-photon semiconducting polymer dot (BF@Pdots) with dual-targeting (cancer cells and mitochondrial) and dual-emission in green and red regions, which is rationally designed through a four-step engineering strategy by using two newly synthesized functionalized polymers PFNA and FD-PSMA as precursors, has been developed for accurate tracking of the dynamic variation of SO2 and FA in the mitochondria of cancer cells. The sensing mechanism is on the basis of the fluorescence resonance energy transfer (FRET) process in BF@Pdots tuned by the reversible Michael addition reaction between the sensing-groups and SO2 (or FA). The integrated BF@Pdots nanoprobes display excellent performances in the accurate detection of the dynamic fluctuation of SO2 and FA such as precise positioning in the mitochondria of cancer cells, self-calibrating ratiometric, two-photon emission with long wavelength excitation, and fast reversible response. The BF@Pdots nanoprobes are also applied to the ratiometric detection of the dynamic fluctuation of exogenous and endogenous SO2 and FA in the mitochondria of cancer cells for the first time with satisfactory results. Taken together, this work will provide an attractive way to develop versatile integrated Pdots-based fluorescent probes through flexible molecular engineering for applications in accurate imaging of biomolecules in living systems.
Assuntos
Corantes Fluorescentes/química , Formaldeído/análise , Mitocôndrias/metabolismo , Polímeros/química , Pontos Quânticos/química , Dióxido de Enxofre/análise , Animais , Linhagem Celular Tumoral , Fluorenos/química , Fluorenos/efeitos da radiação , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/efeitos da radiação , Formaldeído/metabolismo , Humanos , Limite de Detecção , Masculino , Camundongos , Naftalimidas/química , Naftalimidas/efeitos da radiação , Neoplasias/metabolismo , Fótons , Polímeros/efeitos da radiação , Pontos Quânticos/efeitos da radiação , Células RAW 264.7 , Semicondutores , Dióxido de Enxofre/metabolismo , Peixe-ZebraRESUMO
Xanthan gum (XG) and polyvinylpyrrolidone (PVP) are two polymers with low toxicity, high biocompatibility, biodegradability, and high hydrophilicity, making them promising candidates for multiple medical aspects. The present work aimed to synthesize a hydrogel from a mixture of XG and PVP and crosslinked by gamma irradiation. We assessed the hydrogel through a series of physicochemical (FT-IR, TGA, SEM, and percentage of swelling) and biological (stability of the hydrogel in cell culture medium) methods that allowed to determine its applicability. The structural evaluation by infrared spectrum demonstrated that a crosslinked hydrogel was obtained from the combination of polymers. The calorimetric test and swelling percentage confirmed the formation of the bonds responsible for the crosslinked structure. The calorimetric test evidenced that the hydrogel was resistant to decomposition in contrast to non- irradiated material. The determination of the swelling degree showed constant behavior over time, indicating a structure resistant to hydrolysis. This phenomenon also occurred during the test of stability in a cell culture medium. Additionally, microscopic analysis of the sample revealed an amorphous matrix with the presence of porosity. Thus, the findings reveal the synthesis of a novel material that has desirable attributes for its potential application in pharmaceutical and biomedical areas.
Assuntos
Raios gama , Hidrogéis/efeitos da radiação , Polímeros/efeitos da radiação , Polissacarídeos Bacterianos/efeitos da radiação , Povidona/efeitos da radiação , Hidrogéis/síntese química , Hidrogéis/química , Microscopia Eletrônica de Varredura , Modelos Químicos , Estrutura Molecular , Polímeros/síntese química , Polímeros/química , Polissacarídeos Bacterianos/síntese química , Polissacarídeos Bacterianos/química , Porosidade , Povidona/síntese química , Povidona/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Temperatura , Termogravimetria/métodosRESUMO
Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.
Assuntos
Antineoplásicos/farmacologia , Monóxido de Carbono/metabolismo , Corantes Fluorescentes/farmacologia , Nanopartículas Metálicas/química , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Antineoplásicos/toxicidade , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Fluoretos/química , Fluoretos/farmacologia , Fluoretos/efeitos da radiação , Fluoretos/toxicidade , Células HeLa , Humanos , Indóis/química , Indóis/farmacologia , Indóis/efeitos da radiação , Indóis/toxicidade , Raios Infravermelhos , Compostos de Ferro/química , Compostos de Ferro/farmacologia , Compostos de Ferro/efeitos da radiação , Compostos de Ferro/toxicidade , Nanopartículas Metálicas/efeitos da radiação , Nanopartículas Metálicas/toxicidade , Microscopia Confocal , Microscopia de Fluorescência , Terapia Fototérmica , Polímeros/química , Polímeros/farmacologia , Polímeros/efeitos da radiação , Polímeros/toxicidade , Porosidade , Túlio/química , Túlio/farmacologia , Túlio/efeitos da radiação , Túlio/toxicidade , Itérbio/química , Itérbio/farmacologia , Itérbio/efeitos da radiação , Itérbio/toxicidade , Ítrio/química , Ítrio/farmacologia , Ítrio/efeitos da radiação , Ítrio/toxicidadeRESUMO
Herein, novel rodlike CdTe@MPA-PDA particles based on polydopamine (PDA) loaded with CdTe quantum dots (QDs) capped with mercaptopropionic acid (CdTe@MPA QDs) with atypical chemical features are evaluated as a potential actuator for photothermal therapy and oxidative stress induction. Under mild conditions established for the safe and efficient use of lasers, temperature increases of 10.2 and 7.8 °C, photothermal conversion efficiencies of 37.7 and 26.2%, and specific absorption rates of 99 and 69 W/g were obtained for CdTe@MPA-PDA and traditional PDA particles in water, respectively. The particles were set to interact with the human breast adenocarcinoma cell line MDA-MB-231. A significant cellular uptake with the majority of particles colocalized into the lysosomes was obtained at a concentration of 100 µg/mL after 24 h. Additionally, CdTe@MPA-PDA and CdTe@MPA QDs showed significantly different internalization levels and loading kinetics profiles. For the first time, the thermal lens technique was used to demonstrate the stability of particle-like CdTe@MPA-PDA after heating at pH 7 and their migration within the heating region due to the thermodiffusion effect. However, under acidic pH-type lysosomes, a performance decrease in heating was observed, and the chemical feature of the particles was damaged as well. Besides, the internalized rodlike CdTe@MPA-PDA notably enhanced the induction of oxidative stress compared with PDA alone and CdTe@MPA QDs in MDA-MB-231 cells initiating apoptosis. Combining these effects suggests that after meticulous optimizations of the conditions, the CdTe@MPA-PDA particles could be used as a photothermal agent under mild conditions and short incubation time, allowing cytoplasmatic subcellular localization. On the other hand, the same particles act as cell killers by triggering reactive oxygen species after a longer incubation time and lysosomal subcellular localization due to the pH effect on the chemical morphology features of the CdTe@MPA-PDA particles.
Assuntos
Antineoplásicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos/química , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Compostos de Cádmio/química , Compostos de Cádmio/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis/química , Indóis/efeitos da radiação , Luz , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Pontos Quânticos/efeitos da radiação , Telúrio/química , Telúrio/efeitos da radiaçãoRESUMO
Solar-driven steam generation has been recognized as a sustainable and low-cost solution to freshwater scarcity using abundant solar energy. To harvest freshwater, various interfacial evaporators with rational designs of photothermal materials and structures have been developed concentrating on increasing the evaporation rate in the past few years. However, pathogenic microorganism accumulation on the evaporators by long-duration contact with natural water resources may lead to the deterioration of water transportation and the reduction of the evaporation rate. Here, we develop cationic photothermal hydrogels (CPHs) based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) and photothermal polypyrrole (PPy) with bacteria-inhibiting capability for freshwater production via solar-driven steam generation. A rapid water evaporation rate of 1.592 kg m-2 h-1 under simulated solar irradiation is achieved with CPHs floating on the water surface. Furthermore, we find that CPHs possess nearly 100% antibacterial performance against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The significant bacteria-inhibiting capability is mainly attributed to the large number of ammonium groups on the CPH network. Moreover, we show that CPHs exhibit good applicability with stable evaporation in natural lake water over 2 weeks, and the number of bacteria in purified lake water is significantly reduced. The device based on CPHs can achieve â¼0.49 kg m-2 h-1 freshwater production from lake water under natural sunlight. This study provides an attractive strategy for the evaporator to inhibit biological contamination and a potential way for long-term stable freshwater production from natural water resources in practical application.
Assuntos
Antibacterianos/farmacologia , Água Doce/química , Hidrogéis/farmacologia , Vapor , Antibacterianos/química , Antibacterianos/efeitos da radiação , Escherichia coli/química , Hidrogéis/química , Hidrogéis/efeitos da radiação , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/química , Metacrilatos/farmacologia , Polímeros/química , Polímeros/farmacologia , Polímeros/efeitos da radiação , Pirróis/química , Pirróis/farmacologia , Pirróis/efeitos da radiação , Energia Solar , Staphylococcus aureus/efeitos dos fármacos , Luz Solar , Purificação da Água/métodosRESUMO
Surface modification of superparamagnetic Fe3O4 nanoparticles using polymers (polyaniline/polypyrrole) was done by radio frequency (r.f.) plasma polymerization technique and characterized by XRD, TEM, TG/DTA and VSM. Surface-passivated Fe3O4 nanoparticles with polymers were having spherical/rod-shaped structures with superparamagnetic properties. Broad visible photoluminescence emission bands were observed at 445 and 580 nm for polyaniline-coated Fe3O4 and at 488 nm for polypyrrole-coated Fe3O4. These samples exhibit good fluorescence emissions with L929 cellular assay and were non-toxic. Magnetic hyperthermia response of Fe3O4 and polymer (polyaniline/polypyrrole)-coated Fe3O4 was evaluated and all the samples exhibit hyperthermia activity in the range of 42-45 °C. Specific loss power (SLP) values of polyaniline and polypyrrole-coated Fe3O4 nanoparticles (5 and 10 mg/ml) exhibit a controlled heat generation with an increase in the magnetic field.
Assuntos
Compostos de Anilina/química , Diagnóstico por Imagem/métodos , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Polímeros/química , Pirróis/química , Compostos de Anilina/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/efeitos da radiação , Humanos , Campos Magnéticos , Magnetismo/métodos , Nanopartículas de Magnetita/efeitos da radiação , Nanopartículas de Magnetita/uso terapêutico , Teste de Materiais , Gases em Plasma/química , Polímeros/efeitos da radiação , Pirróis/efeitos da radiação , Ondas de Rádio , Propriedades de Superfície/efeitos da radiação , Difração de Raios XRESUMO
The lack of cancer cell specificity and the occurrence of multidrug resistance (MDR) are two major obstacles in the treatment of hepatocellular carcinoma (HCC). To tackle these challenges, a novel nanoparticle (NP)-based drug delivery system (DDS) with a core/shell structure consisted of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-galactose (Gal)/polydopamine (PDA) is fabricated. The NP is loaded with doxorubicin (DOX) and a nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN) sensitive to heat to afford NO-DOX@PDA-TPGS-Gal. The unique binding of Gal to asialoglycoprotein receptor (ASGPR) and the pH-sensitive degradation of NP ensure the targeted transportation of NP into liver cells and the release of DOX in HCC cells. The near-infrared (NIR) light further facilitates DOX release and initiates NO generation from BNN due to the photothermal property of PDA. In addition to the cytotoxicity contributed by DOX, NO, and heat, TPGS and NO act as MDR reversal agents to inhibit P-glycoprotein (P-gp)-related efflux of DOX by HepG2/ADR cells. The combined chemo-photothermal therapy (chemo-PTT) by NO-DOX@PDA-TPGS-Gal thus shows potent anti-cancer activity against drug-resistant HCC cells in vitro and in vivo and significantly prolongs the life span of drug-resistant tumor-bearing mice. The present work provides a useful strategy for highly targeted and MDR reversal treatment of HCC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Neoplasias Hepáticas/tratamento farmacológico , Doadores de Óxido Nítrico/uso terapêutico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Tratamento Farmacológico , Galactose/química , Humanos , Indóis/química , Indóis/efeitos da radiação , Raios Infravermelhos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/efeitos da radiação , Doadores de Óxido Nítrico/química , Compostos Nitrosos/química , Compostos Nitrosos/uso terapêutico , Terapia Fototérmica , Polímeros/química , Polímeros/efeitos da radiação , Ratos Sprague-Dawley , Vitamina E/química , Vitamina E/efeitos da radiação , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O2 self-supply, self-sufficient singlet oxygen (1O2), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia. The production of O2 can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment in situ mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.
Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Portadores de Fármacos/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Camptotecina/química , Camptotecina/uso terapêutico , Catálise/efeitos da radiação , Linhagem Celular Tumoral , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Feminino , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Luz , Azul de Metileno/análogos & derivados , Azul de Metileno/efeitos da radiação , Camundongos Endogâmicos BALB C , Nanoestruturas/efeitos da radiação , Neoplasias/metabolismo , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Platina/química , Platina/efeitos da radiação , Polímeros/síntese química , Polímeros/química , Polímeros/efeitos da radiação , Porosidade , Oxigênio Singlete/metabolismo , Nanomedicina TeranósticaRESUMO
In this study, a novel class of multifunctional responsive nanoparticles is designed and fabricated as drug nanocarriers for synergetic chemo-photothermal therapy of tumors. The proposed nanoparticles are composed of a thermo-/pH-responsive poly(N-isopropylacrylamide-co-acrylic acid) (PNA) nanogel core, a polydopamine (PDA) layer for photothermal conversion, and an outer folic acid (FA) layer as a targeting agent for the folate receptors on tumor cells. The fabricated nanoparticles show good biocompatibility and outstanding photothermal conversion efficiency. The proposed nanoparticles loaded with doxorubicin (DOX) drug molecules are stable under physiological conditions with low leakage of drugs, while rapidly release drugs in environments with low pH conditions and at high temperature. The experimental results show that the drug release process is mainly governed by Fickian diffusion. In vitro cell experimental results demonstrate that the PNA-DOX@PDA-FA nanoparticles can be phagocytized by 4T1 tumor cells and release drugs in tumor cell acidic environments, and confirm that the combined chemo and photothermal therapeutic efficacy of PNA-DOX@PDA-FA nanoparticles is higher than the photothermal therapeutic efficacy or the chemotherapeutic efficacy alone. The proposed multifunctional responsive nanoparticles in this study provide a novel class of drug nanocarriers as a promising tool for synergetic chemo-photothermal therapy of tumors.
Assuntos
Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Nanopartículas Multifuncionais/química , Acrilamidas/química , Acrilamidas/metabolismo , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/metabolismo , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Endocitose/fisiologia , Ácido Fólico/análogos & derivados , Ácido Fólico/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Indóis/metabolismo , Indóis/efeitos da radiação , Raios Infravermelhos , Camundongos , Nanopartículas Multifuncionais/metabolismo , Terapia Fototérmica , Polímeros/química , Polímeros/metabolismo , Polímeros/efeitos da radiação , TemperaturaRESUMO
A π-conjugated porous organic polymer (BCzBz) was fabricated employing N,N'-bicarbazole and benzothiadiazole as molecular building units exhibiting broad visible light absorption. The photostable, water-dispersible, and cytocompatible BCzBz was demonstrated as an efficient probe for intracellular reactive oxygen species generation under photoirradiation.
Assuntos
Antineoplásicos/farmacologia , Carbazóis/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiadiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Carbazóis/síntese química , Carbazóis/efeitos da radiação , Células HeLa , Humanos , Luz , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/síntese química , Polímeros/efeitos da radiação , Porosidade , Tiadiazóis/síntese química , Tiadiazóis/efeitos da radiaçãoRESUMO
Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. This strategy provides a facile method for developing biomimetic hydrogels with high antibacterial capability.
Assuntos
Antibacterianos/farmacologia , Hidrogéis/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Polímeros/farmacologia , Tiadiazóis/farmacologia , Tiofenos/farmacologia , Antibacterianos/química , Antibacterianos/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/efeitos da radiação , Escherichia coli/efeitos dos fármacos , Fluoresceínas/química , Fluoresceínas/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Hidrogéis/química , Hidrogéis/efeitos da radiação , Luz , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/química , Polímeros/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Tiadiazóis/química , Tiadiazóis/efeitos da radiação , Tiofenos/química , Tiofenos/efeitos da radiaçãoRESUMO
In this work, an iron self-boosting polymer nanoenzyme was prepared by using pyrrole-3-carboxylic acid as a monomer and iron as an oxidizing agent via a simple and one-step method [hereafter referred to as FePPy nanoparticles (NPs)]. In fact, researchers previously paid negligible attention on the iron element during the polymerization reaction of polypyrrole, thus the intrinsically catalytic functions and enzymatic activities of the high iron content (wt %: 21.11%) are ignored and not fully explored. As expected, results demonstrate that the as-synthesized FePPy NPs can decompose H2O2 to generate hydroxyl radicals (â¢OH) which exhibit enzyme characteristics, further inducing a nonapoptotic ferroptosis pathway. Moreover, the nanoenzyme shows impressive photothermal properties which can accelerate the Fenton reactions to enhance ferroptosis. The combined photothermal and ferroptosis therapy of FePPy NPs was found to have high efficacy. With the properties of easy synthesis, high efficacy, and good biocompatibility, the FePPy NPs are considered as potential agents for cancer treatments.
Assuntos
Antineoplásicos/uso terapêutico , Ferroptose/efeitos dos fármacos , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Ácidos Carboxílicos/química , Ácidos Carboxílicos/efeitos da radiação , Ácidos Carboxílicos/uso terapêutico , Catálise , Feminino , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/metabolismo , Ferro/química , Ferro/efeitos da radiação , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/uso terapêutico , Pirróis/química , Pirróis/efeitos da radiação , Pirróis/uso terapêutico , TemperaturaRESUMO
Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparin-decorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesion-site-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.
Assuntos
Quitosana/uso terapêutico , Heparina/uso terapêutico , Nanopartículas/uso terapêutico , Polímeros/uso terapêutico , Pirróis/uso terapêutico , Trombose/tratamento farmacológico , Animais , Quitosana/química , Células Endoteliais/metabolismo , Heparina/química , Heparina/metabolismo , Luz , Masculino , Camundongos Endogâmicos ICR , Nanopartículas/química , Nanopartículas/efeitos da radiação , Selectina-P/metabolismo , Fototerapia/métodos , Polímeros/química , Polímeros/efeitos da radiação , Pirróis/química , Pirróis/efeitos da radiação , Terapia Trombolítica/métodos , Trombose/metabolismoRESUMO
BACKGROUND: The research aims to study the effect of circumferential compliance of synthetic vascular prostheses on their healing during implantation in the infrarenal abdominal aorta of pigs. METHODS: In an experiment, 12 pigs were implanted with blood vessel prostheses in the infrarenal abdominal aorta. The prostheses possessed elastic characteristics obtained by a tensile testing machine, and differed in circumferential compliance: rigid (polycaprolactone [PCL]); less compliant than the native aorta (polyurethane [PU]); comparable in compliance to the native aorta (copolymer of vinylidene fluoride with hexafluoropropylene) before (FKM) and after radiation treatment (FKM-γ). The implanted prostheses compliance was measured by aortography during the first 3 days and 1 month after implantation, the condition of the prosthesis capsule was evaluated by macroscopic preparations and histologic examination. RESULTS: Pulsation on PCL prostheses was nonexistent immediately after implantation. On PU prostheses, slight pulsation was noted during the first 3 days and disappeared after 1 month. On FKM prostheses, although pulsation persisted after 1 month, a significant expansion of prostheses was also recorded as a result of fatigue plastic deformation. On FKM-γ prostheses, pulsation comparable in magnitude with aortic pulsation was present 1 month after implantation with no change in the size of the prosthesis. Macroscopic preparations reveal significant differences in the formed connective tissue capsule. The PCL prosthesis capsule is thick, narrowing the lumen of the vessel from the outside. The outer surface of PU prostheses is covered with a thinner uniform fibrous capsule. The inner surface of the FKM and FKM-γ prostheses is covered with a thin layer of smooth whitish tissue. The FKM prosthesis, unlike the FKM-γ prosthesis, is sharply expanded. In all cases, moderate aortic expansion was observed distal to the prosthesis. According to the histologic data, the outer and inner capsules of PCL prostheses are covered with a thick layer of fibrous tissue with signs of productive inflammation and foci of calcification. PU prostheses are surrounded by a thick connective tissue capsule partially endothelialized from the inside; the outer capsule is randomly populated with fibroblastic cells. FKM prostheses have a thin outer capsule where smooth muscle cells are visible, mainly oriented along and across the prosthesis axis; the inner capsule is thin and completely covered with a layer of endothelial cells from the side of the lumen. A layered structure is visible in the prosthesis capsule of FKM-γ, and the fibroblast cells in each layer of the capsule are oriented along or across the prosthesis axis, similar to the structure of a natural arterial vessel. The inner surface of the prosthesis is completely endothelialized. CONCLUSIONS: The healing and degree of inflammation in a capsule of blood vessel prostheses implanted in the infrarenal abdominal aorta of pigs depend on the degree of their circumferential compliance. Although maintaining pulsations, the cellular structure of the capsule is characterized by a greater degree of differentiation and approaches the structure of the native arterial wall.
Assuntos
Aorta Abdominal/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Polímeros/química , Desenho de Prótese , Animais , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/patologia , Raios gama , Teste de Materiais , Modelos Animais , Maleabilidade , Poliésteres/química , Polímeros/efeitos da radiação , Poliuretanos/química , Polivinil/química , Sus scrofa , Resistência à Tração , Fatores de Tempo , Remodelação Vascular , CicatrizaçãoRESUMO
In the present study, we examined the inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by synthetic conjugated polymers and oligomers developed in our laboratories as antimicrobials for bacteria, fungi, and nonenveloped viruses. The results show highly effective light-induced inactivation with several of these oligomers and polymers including irradiation with near-UV and visible light. In the best case, one oligomer induced a 5-log reduction in pfu/mL within 10 min. In general, the oligomers are more active than the polymers; however, the polymers are active with longer wavelength visible irradiation. Although not studied quantitatively, the results show that in the presence of the agents at concentrations similar to those used in the light studies, there is essentially no dark inactivation of the virus. Because three of the five materials/compounds examined are quaternary ammonium derivatives, this study indicates that conventional quaternary ammonium antimicrobials may not be active against SARS-CoV-2. Our results suggest several applications involving the incorporation of these materials in wipes, sprays, masks, and clothing and other personal protection equipment that can be useful in preventing infections and the spreading of this deadly virus and future outbreaks from similar viruses.
Assuntos
Tratamento Farmacológico da COVID-19 , Polímeros/farmacologia , SARS-CoV-2/efeitos dos fármacos , Animais , COVID-19/virologia , Chlorocebus aethiops , Humanos , Luz , Polímeros/efeitos da radiação , SARS-CoV-2/patogenicidade , SARS-CoV-2/efeitos da radiação , Raios Ultravioleta , Células Vero , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiaçãoRESUMO
As a critical component for photodynamic therapy toward cancer treatment, photosensitizers require high photoinduced reactive oxygen species generation efficiency, good biocompatibility, and high phototoxicity. Herein, a series of donor-acceptor conjugated polymers containing dibenzothiophene-S,S-dioxide derivatives are designed and synthesized, which can be used as effective photosensitizers. The resulting copolymer PTA5 shows strong green light emission with high photoluminescence quantum yields owing to the intercrossed excited state of local existed and charge transfer states. The PTA5 nanoparticles can be fabricated by encapsulation with a biocompatible polymer matrix. Upon excitation at 800 nm, these nanoparticles present a relatively large two-photon absorption cross section of 3.29 × 106 GM. These nanoparticles also exhibit good photostability in water and thus can be utilized for bioimaging. The tissue-penetrating depths of up to 170 µm for hepatic vessels and 380 µm for blood vessels of mouse ear were achieved using PTA5 nanoparticles. Furthermore, PTA5 nanoparticles show impressive reactive oxygen species generation capability under the irradiation of a white light source. This can be attributed to the effective intersystem crossing between high-level excited state. Upon irradiation with white light (400-700 nm) at 50 mW cm-2 for 5 min every other day, the tumor growth can be effectively suppressed in the presence of PTA5 nanoparticles. These findings demonstrate that PTA5 nanoparticles can be used as a photosensitizer for photodynamic therapy.
Assuntos
Óxidos S-Cíclicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Polímeros/uso terapêutico , Tiofenos/uso terapêutico , Compostos de Anilina/síntese química , Compostos de Anilina/efeitos da radiação , Compostos de Anilina/uso terapêutico , Animais , Óxidos S-Cíclicos/síntese química , Óxidos S-Cíclicos/efeitos da radiação , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/uso terapêutico , Células HeLa , Humanos , Camundongos , Nanopartículas/efeitos da radiação , Imagem Óptica , Fotoquimioterapia , Fótons , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Polímeros/síntese química , Polímeros/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Tiofenos/síntese química , Tiofenos/efeitos da radiaçãoRESUMO
Polypyrrole one-dimensional nanostructures (nanotubes, nanobelts and nanofibers) were prepared using three various dyes (Methyl Orange, Methylene Blue and Eriochrome Black T). Their high electrical conductivity (from 17.1 to 60.9 S cm-1), good thermal stability (in the range from 25 to 150 °C) and resistivity against ageing (half-time of electrical conductivity around 80 days and better) were used in preparation of lightweight and flexible composites with silicone for electromagnetic interference shielding in the C-band region (5.85-8.2 GHz). The nanostructures' morphology and chemical structure were characterized by scanning electron microscopy, Brunauer-Emmett-Teller specific surface measurement and attenuated total reflection Fourier-transform infrared spectroscopy. DC electrical conductivity was measured using the Van der Pauw method. Complex permittivity and AC electrical conductivity of respective silicone composites were calculated from the measured scattering parameters. The relationships between structure, electrical properties and shielding efficiency were studied. It was found that 2 mm-thick silicone composites of polypyrrole nanotubes and nanobelts shield almost 80% of incident radiation in the C-band at very low loading of conductive filler in the silicone (5% w/w). Resulting lightweight and flexible polypyrrole composites exhibit promising properties for shielding of electromagnetic interference in sensitive biological and electronic systems.
Assuntos
Radiação Eletromagnética , Nanoestruturas/química , Polímeros/química , Pirróis/química , Silicones/química , Compostos Azo/química , Azul de Metileno/química , Microscopia Eletrônica de Varredura , Nanofibras/química , Nanofibras/efeitos da radiação , Nanoestruturas/efeitos da radiação , Nanoestruturas/ultraestrutura , Nanotubos/química , Nanotubos/efeitos da radiação , Nanotubos/ultraestrutura , Polímeros/efeitos da radiação , Pirróis/efeitos da radiação , Silicones/efeitos da radiaçãoRESUMO
Dynamic biochemical and biophysical signals of cellular matrix define and regulate tissue-specific cell functions and fate. To recapitulate this complex environment in vitro, biomaterials based on structural- or degradation-tunable polymers have emerged as powerful platforms for regulating the "on-demand" cell-material dynamic interplay. As one of the most prevalent photoswitch molecules, the photoisomerization of azobenzene demonstrates a unique advantage in the construction of dynamic substrates. Moreover, the development of azobenzene-containing biomaterials is particularly helpful in elucidating cells that adapt to a dynamic microenvironment or integrate spatiotemporal variations of signals. Herein, this minireview, places emphasis on the research progress of azobenzene photoswitches in the dynamic regulation of matrix signals. Some techniques and material design methods have been discussed to provide some theoretical guidance for the rational and efficient design of azopolymer-based material platforms. In addition, considering that the UV-light response of traditional azobenzene photoswitches is not conducive to biological applications, we have summarized the recent approaches to red-shifting the light wavelength for azobenzene activation.
Assuntos
Compostos Azo/química , Microambiente Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Matriz Extracelular/metabolismo , Animais , Compostos Azo/efeitos da radiação , Linhagem Celular Tumoral , Materiais Revestidos Biocompatíveis/efeitos da radiação , Condutividade Elétrica , Humanos , Isomerismo , Luz , Polímeros/química , Polímeros/efeitos da radiação , Propriedades de SuperfícieRESUMO
In this work, polythiophene nanoparticles (PTh-NPs) were synthesized by a surfactant-free oxidative chemical polymerization method at 60 °C, using ammonium persulphate as an oxidant. Various physicochemical properties were studied in terms of field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy, and differential scanning calorimetry (DSC)/thermogravimetric analysis (TGA). Photothermal performance of the as-synthesized PTh-NPs was studied by irradiating near infra-red of 808 nm under different concentration of the substrate and power supply. The photothermal stability of PTh-NPs was also studied. Photothermal effects of the as-synthesized PTh-NPs on colorectal cancer cells (CT-26) were studied at 100 µg/mL concentration and 808 nm NIR irradiation of 2.0 W/cm2 power. Our in vitro results showed remarkable NIR laser-triggered photothermal apoptotic cell death by PTh-NPs. Based on the experimental findings, it is revealed that PTh-NPs can act as a heat mediator and can be an alternative material for photothermal therapy in cancer treatment.
Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Polímeros/farmacologia , Tiofenos/química , Sulfato de Amônio/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/patologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Raios Infravermelhos , Camundongos , Nanopartículas/efeitos da radiação , Nanopartículas/ultraestrutura , Oxirredução , Terapia Fototérmica/métodos , Polimerização , Polímeros/síntese química , Polímeros/efeitos da radiação , Tiofenos/síntese química , Tiofenos/farmacologia , Tiofenos/efeitos da radiaçãoRESUMO
In this research, irradiation by gamma rays was employed as an eco-friendly route for the construction of bimetallic silver-gold nanoparticles (Ag-Au NPs), while Gum Arabic polymer was used as a capping agent. Ag-Au NPs were characterized through UV-Vis., XRD, EDX, HR-TEM, FTIR, SEM/mapping and EDX analysis. Antibiofilm and antimicrobial activities were examined against some bacteria and Candida sp. isolates from diabetic foot patients. Our results revealed that the synthesis of Ag-Au NPs depended on the concentrations of tetra-chloroauric acid and silver nitrate. HR-TEM analysis confirmed the spherical nature and an average diameter of 18.58 nm. FTIR results assured many functional groups in Gum Arabic which assisted in increasing the susceptibility of incorporation with Ag-Au NPs. Our results showed that, Ag-Au NPs exhibited the highest antimicrobial performance against B. subtilis (14.30 mm ZOI) followed by E. coli (12.50 mm ZOI) and C. tropicalis (11.90 mm ZOI). In addition, Ag-Au NPs were able to inhibit the biofilm formation by 99.64%, 94.15%, and 90.79% against B. subtilis, E. coli, and C. tropicalis, respectively. Consequently, based on the promising properties, they showed superior antimicrobial potential at low concentration and continued-phase durability, they can be extensively-used in many pharmaceutical and biomedical applications.