RESUMO
The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions used to link the monomers are crucial because such monomers are normally dynamic and can disassemble during the linking process, leading to mixture of products. Therefore, although noncovalent interactions have been widely introduced into metallacycle structures to prepare metallosupramolecular polymers, metallacycle-cored polymers linked by covalent bonds have been rarely reported. Herein, we used the mild, highly efficient amidation reaction between alkylamine and N-hydroxysuccinimide-activated carboxylic acid to link the pendent amino functional groups of a rhomboidal metallacycle 10 to give metallacycle-cored polymers P1 and P2, which further yielded nanoparticles at low concentration and transformed into network structures as the concentration increased. Moreover, these polymers exhibited enhanced emission and showed better quantum yields than metallacycle 10 in methanol and methanol/water (1/9, vol/vol) due to the aggregation-induced emission properties of a tetraphenylethene-based pyridyl donor, which serves as a precursor for metallacycle 10. The fluorescence properties of these polymers were further used in cell imaging, and they showed a significant enrichment in lung cells after i.v. injection. Considering the anticancer activity of rhomboidal Pt(II) metallacycles, this type of fluorescent metallacycle-cored polymers can have potential applications toward lung cancer treatment.
Assuntos
Rastreamento de Células/métodos , Meios de Contraste/química , Imagem Molecular/métodos , Nanopartículas/química , Fluorescência , Humanos , Polímeros/química , Água/químicaRESUMO
Chemoimmunotherapy, which combines chemotherapeutics with immune-modulating agents, represents an appealing approach for improving cancer therapy. To optimize its therapeutic efficacy, differentially delivering multiple therapeutic drugs to target cells is desirable. Here we developed an immunostimulatory nanocarrier (denoted as BLZ-945SCNs/Pt) that could spatially target tumor-associated macrophages (TAMs) and tumor cells for cancer chemoimmunotherapy. BLZ-945SCNs/Pt undergo supersensitive structure collapse in the prevascular regions of tumor tissues and enable the simultaneous release of platinum (Pt)-prodrug conjugated small particles and BLZ-945, a small molecule inhibitor of colony stimulating factor 1 receptor (CSF-1R) of TAMs. The released BLZ-945 can be preferentially taken up by TAMs to cause TAMs depletion from tumor tissues, while the small particles carrying Pt-prodrug enable deep tumor penetration as well as intracellularly specific drug release to kill more cancer cells. Our studies demonstrate that BLZ-945SCNs/Pt outperform their monotherapy counterparts in multiple tumor models. The underlying mechanism studies suggest that the designer pH-sensitive codelivery nanocarrier not only induces apoptosis of tumor cells but also modulates the tumor immune environment to eventually augment the antitumor effect of CD8+ cytotoxic T cells through TAMs depletion.
Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Macrófagos/efeitos dos fármacos , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Apoptose , Benzotiazóis/administração & dosagem , Benzotiazóis/química , Linhagem Celular Tumoral , Terapia Combinada , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Imunoterapia/métodos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Ácidos Picolínicos/administração & dosagem , Ácidos Picolínicos/química , Platina/química , Polímeros/química , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Propriedades de Superfície , Microambiente TumoralRESUMO
During the process of human civilization, owning household pets has become increasingly popular. However, dogs and cats may be reservoirs or vectors of transmissible diseases to humans. Confronted with the overpopulation of pets, traditional contraception methods, surgical methods of sterilization, for animals are used, namely, ovariohysterectomy and orchidectomy. Therefore, a simple, nonsurgical, controllable, more effective and less expensive contraception method is highly desirable. In this study, we show that in situ testicular injection of methoxy poly(ethylene glycol)-modified gold nanorods with near-infrared irradiation in male mice can achieve short-lived or permanent male infertility. In a lower hyperthermia treatment, the morphology of testes and seminiferous tubules is only partly injured, and fertility indices are decreased to 10% at day 7, then recovered to 50% at day 60. In a higher hyperthermia treatment, the morphology of testes and seminiferous tubules are totally destroyed, and fertility indices are decreased to 0 at day 7. Overall, our results indicate a potential application of plasmonic nanomaterials for male contraception.
Assuntos
Anticoncepção , Ouro/química , Nanotubos/química , Animais , Luz , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , TemperaturaRESUMO
ω-Methoxy and ω-aminoethyl poly(ethylene glycol)-modified 14-nm gold nanoparticles can accumulate in mouse testes, pass through the blood-testis barrier, and enter germ cells. Furthermore, PEG-NH2 @AuNP accumulate more easier in the testes and increase plasma T levels. However, these two gold nanoparticle types have no effect on male fertility, fetal survival, or fetal development.
Assuntos
Fertilidade , Ouro/química , Nanopartículas Metálicas , Testosterona/sangue , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica de TransmissãoRESUMO
Anesthetic isoflurane (ISO) has immunomodulatory effects. In the present study, we investigated whether a subanesthetic dose of ISO (0.7%) protected against zymosan (ZY) induced inflammatory responses in the murine lung and isolated neutrophils. At 1 and 6 hrs after ZY administration intraperitoneally, ISO was inhaled for 1 hr, and 24 hrs later, lung inflammation and injury were assessed. We found that ISO improved the survival rate of mice and mitigated lung injury as characterized by the histopathology, wet-to-dry weight ratio, protein leakage, and lung function index. ISO significantly attenuated ZY-induced lung neutrophil recruitment and inflammation. This was suggested by the downregulation of (a) endothelial adhesion molecule expression and myeloperoxidase (MPO) activity in lung tissue and polymorphonuclear neutrophils (b) chemokines, and (c) proinflammatory cytokines in BALF. Furthermore, ZY-induced nuclear translocation and DNA-binding activity of NF- κ B p65 were also reduced by ISO. ISO treatment inhibited iNOS expression and activity, as well as subsequent nitric oxide generation. Consistent with these in vivo observations, in vitro studies confirmed that ISO blocked NF- κ B and iNOS activation in primary mouse neutrophils challenged by ZY. These results provide evidence that 0.7% ISO ameliorates inflammatory responses in ZY-treated mouse lung and primary neutrophils.
Assuntos
Isoflurano/administração & dosagem , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Neutrófilos/imunologia , Pneumonia/tratamento farmacológico , Zimosan/efeitos adversos , Transporte Ativo do Núcleo Celular , Animais , Gasometria , Líquido da Lavagem Broncoalveolar , Quimiocinas/metabolismo , Citocinas/metabolismo , Regulação para Baixo , Concentração de Íons de Hidrogênio , Inflamação/patologia , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/mortalidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Neutrófilos/citologia , Neutrófilos/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Nitritos/metabolismo , Peroxidase/metabolismo , Fatores de TempoRESUMO
Formononetin (FMNT) is an isoflavone found in many herbs including Trifolium pratense L., Spatholobus suberectus Dunn., and Astragalus mongholicus Bunge. The purpose of this study is to investigate pharmacological properties of FMNT on neurotoxicity induced by N-methyl-D-asparate (NMDA) in primary-cultured cortical neurons. The cell viability was significantly decreased after exposure to NMDA (200 µM) for 40 min. Pretreatment of FMNT (10 µM) for 12 h significantly attenuated the cell loss induced by NMDA exposure. Flow cytometry analysis revealed that treatment of FMNT attenuated the number of apoptotic cells, especially the early phase apoptotic cells, induced by NMDA exposure. Western blot analysis showed that FMNT regulated the expression of apoptosis-related proteins by increasing the levels of Bcl-2 and pro-caspase-3 and decreasing the levels of Bax and caspase-3. These findings demonstrate that FMNT is capable of protecting neurons from NMDA-evoked excitotoxic injury and has a potential perspective to the clinical treatment for neurodegenerative disorders in central nervous system.
Assuntos
Apoptose/efeitos dos fármacos , Isoflavonas/farmacologia , N-Metilaspartato/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Animais , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/citologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
We report a new strategy for differential delivery of antimicrobials to bacterial infection sites with a lipase-sensitive polymeric triple-layered nanogel (TLN) as the drug carrier. The TLN was synthesized by a convenient arm-first procedure using an amphiphilic diblock copolymer, namely, monomethoxy poly(ethylene glycol)-b-poly(ε-caprolactone), to initiate the ring-opening polymerization of the difunctional monomer 3-oxapentane-1,5-diyl bis(ethylene phosphate). The hydrophobic poly(ε-caprolactone) (PCL) segments collapsed and surrounded the polyphosphoester core, forming a hydrophobic and compact molecular fence in aqueous solution which prevented antibiotic release from the polyphosphoester core prior to reaching bacterial infection sites. However, once the TLN sensed the lipase-secreting bacteria, the PCL fence of the TLN degraded to release the antibiotic. Using Staphylococcus aureus (S. aureus) as the model bacterium and vancomycin as the model antimicrobial, we demonstrated that the TLN released almost all the encapsulated vancomycin within 24 h only in the presence of S. aureus, significantly inhibiting S. aureus growth. The TLN further delivered the drug into bacteria-infected cells and efficiently released the drug to kill intracellular bacteria. This technique can be generalized to selectively deliver a variety of antibiotics for the treatment of various infections caused by lipase-secreting bacteria and thus provides a new, safe, effective, and universal approach for the treatment of extracellular and intracellular bacterial infections.
Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Lipase/metabolismo , Polietilenoglicóis/química , Polietilenoimina/química , Polímeros/química , Antibacterianos/farmacologia , Portadores de Fármacos/metabolismo , Lipase/química , Testes de Sensibilidade Microbiana , Nanogéis , Polietilenoglicóis/metabolismo , Polietilenoimina/metabolismo , Polímeros/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade , Vancomicina/farmacologiaRESUMO
OBJECTIVE: To investigate the therapeutical effects of KANGFUXINYE on the upper gastrointestinal injury induced by paraquat in rats, and to explore the proper mechanism. METHODS: A total of 120 adult Wistar male rats were randomly divided into three groups, control group (CG), model group (MG) and treatment group (TG), 40 rats each group. The MG and TG were given 20% paraquat 50 mg/kg by oral administration, after 2 h the TG was given KANGFUXINYE solution 1.5 ml by oral administration, 3 times a day. The CG was given normal saline. On the 3rd, 6th, 9th, 12th and 15th days after exposure, 8 rats of each group were killed respectively, and the tissues from esophagus and stomach were collected and examined by HE staining for observing the mucosa injury. The superoxide dismutase (SOD) and malondialdehyde (MDA) of serum were detected. RESULTS: On the 3rd, 6th, 9th, 12th and 15th days after exposure, the results of pathological examination showed that the mucosa injury in TG was significantly relieved as compared with MG, the activity of serum SOD reduced obviously and the MDA levels increased significantly in MG, as compared with CG (P<0.05). The activity of serum SOD increased obviously and the MDA levels decreased significantly in TG, as compared with MG (P<0.05). CONCLUSION: The results of present indicate that KANGFUXINYE has the therapeutical effects on the upper gastrointestinal injury caused by paraquat in rats. The mechanism of therapeutical effects may be due to the increasing SOD activity, eliminating free radicles and inhibiting the lipid peroxidation.
Assuntos
Produtos Biológicos/uso terapêutico , Gastroenteropatias/terapia , Paraquat/intoxicação , Animais , Modelos Animais de Doenças , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismoRESUMO
Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. The intracellular accumulation of drug and the intracellular release of drug molecules from the carrier could be the most important barriers for nanoscale carriers in overcoming MDR. We demonstrated that the redox-responsive micellar nanodrug carrier assembled from the single disulfide bond-bridged block polymer of poly(ε-caprolactone) and poly(ethyl ethylene phosphate) (PCL-SS-PEEP) achieved more drug accumulation and retention in MDR cancer cells. Such drug carrier rapidly released the incorporated doxorubicin (DOX) in response to the intracellular reductive environment. It therefore significantly enhanced the cytotoxicity of DOX to MDR cancer cells. It was demonstrated that nanoparticular drug carrier with either poly(ethylene glycol) or poly(ethyl ethylene phosphate) (PEEP) shell increased the influx but decreased the efflux of DOX by the multidrug resistant MCF-7/ADR breast cancer cells, in comparison with the direct incubation of MCF-7/ADR cells with DOX, which led to high cellular retention of DOX. Nevertheless, nanoparticles bearing PEEP shell exhibited higher affinity to the cancer cells. The shell detachment of the PCL-SS-PEEP nanoparticles caused by the reduction of intracellular glutathione significantly accelerated the drug release in MCF-7/ADR cells, demonstrated by the flow cytometric analyses, which was beneficial to the entry of DOX into the nuclei of MCF-7/ADR cells. It therefore enhanced the efficiency in overcoming MDR of cancer cells, which renders the redox-responsive nanoparticles promising in cancer therapy.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Dissulfetos/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Poliésteres/química , Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , OxirreduçãoRESUMO
In this study, we investigated the role of embryonic gene Cripto-1 (CR-1) in hepatocellular carcinoma (HCC) using hepatocyte-specific CR-1-overexpressing transgenic mice. The expression of truncated 1.7-kb CR-1 transcript (SF-CR-1) was significantly higher than the full-length 2.0-kb CR-1 transcript (FL-CR-1) in a majority of HCC tissues and cell lines. Moreover, CR-1 mRNA and protein levels were significantly higher in HCC tissues than adjacent normal liver tissues. Hepatocyte-specific over-expression of CR-1 in transgenic mice enhanced hepatocyte proliferation after 2/3 partial hepatectomy (2/3 PHx). CR-1 over-expression significantly increased in vivo xenograft tumor growth of HCC cells in nude mice and in vitro HCC cell proliferation, migration, and invasion. CR-1 over-expression in the transgenic mouse livers deregulated HCC-related signaling pathways such as AKT, Wnt/ß-catenin, Stat3, MAPK/ERK, JNK, TGF-ß and Notch, as well as expression of HCC-related genes such as CD5L, S100A8, S100A9, Timd4, Orm2, Orm3, PDK4, DMBT1, G0S2, Plk2, Plk3, Gsta1 and Gsta2. However, histological signs of precancerous lesions, hepatocyte dysplasia or HCC formation were not observed in the livers of 3-, 6- or 8-month-old hepatocyte-specific CR-1-overexpressing transgenic mice. These findings demonstrate that liver-specific CR-1 overexpression in transgenic mice deregulates signaling pathways and genes associated with HCC.
Assuntos
Carcinoma Hepatocelular/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Proteínas Ligadas por GPI/metabolismo , Hepatócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Carcinogênese , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Fator de Crescimento Epidérmico/genética , Proteínas Ligadas por GPI/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Hepáticas , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Nus , Camundongos Transgênicos , Proteínas de Neoplasias/genética , Neoplasias Experimentais , Especificidade de Órgãos , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: Hydroxysafflor Yellow A (HSYA), which is one of the most important active ingredients of the Chinese herb Carthamus tinctorius L, is widely used in the treatment of cerebrovascular and cardiovascular diseases. However, the potential protective effect of HSYA in spinal cord ischemia/reperfusion (I/R) injury is still unknown. METHODS: Thirty-nine rabbits were randomly divided into three groups: sham group, I/R group and HSYA group. All animals were sacrificed after neurological evaluation with modified Tarlov criteria at the 48th hour after reperfusion, and the spinal cord segments (L4-6) were harvested for histopathological examination, biochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. RESULTS: Neurological outcomes in HSYA group were slightly improved compared with those in I/R group. Histopathological analysis revealed that HSYA treatment attenuated I/R induced necrosis in spinal cords. Similarly, alleviated oxidative stress was indicated by decreased malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity after HSYA treatment. Moreover, as seen from TUNEL results, HSYA also protected neurons from I/R-induced apoptosis in rabbits. CONCLUSIONS: These findings suggest that HSYA may protect spinal cords from I/R injury by alleviating oxidative stress and reducing neuronal apoptosis in rabbits.
Assuntos
Chalcona/análogos & derivados , Fármacos Neuroprotetores , Quinonas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Traumatismos da Medula Espinal/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Chalcona/farmacologia , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coelhos , Traumatismo por Reperfusão/patologia , Traumatismos da Medula Espinal/patologia , Isquemia do Cordão Espinal/patologia , Superóxido Dismutase/metabolismoRESUMO
Reversibly cross-linked core-shell-corona micelles based on a triblock copolymer composed of poly(aliphatic ester), polyphosphoester, and poly(ethylene glycol) are reported. The triblock copolymer is synthesized through consecutive ring-opening polymerization of ε-caprolactone and 2,4-dinitrophenylthioethyl ethylene phosphate, followed by conjugation of poly(ethylene glycol). After deprotection under mild conditions, the amphiphilic polymer forms core-shell-corona micelles with free thiols in the shell. Cross-linking of the micelles within the shell reduces their critical micellization concentration and enhances their stability against severe conditions. The redox-sensitive cross-linkage allows the facilitated release of entrapped anticancer drugs in the cytoplasm in response to the intracellular reductive environment. With enhanced stability during circulation after administration, and accelerated intracellular drug release at the target site, the biocompatible and biodegradable shell-cross-linked polymeric micelle is promising as a drug vehicle for cancer chemotherapy.
RESUMO
The surface hydrophilicity of nanoparticles has a major impact on their biological fates. Ascertaining the correlation between nanoparticle surface hydrophilicity and their biological behaviors is particularly instructive for future nanomedicine design and their antitumor efficacy optimization. Herein, we designed a series of polymeric nanoparticles based on polyphosphoesters with well-controlled surface hydrophilicity in the molecular level and systemically evaluated their biological behaviors. The results demonstrated that high surface hydrophilicity preferred lower protein absorption, better stability, longer blood circulation, and higher tumor accumulation but lower cellular uptake. Upon encapsulation of drugs, nanoparticles with high hydrophilicity showed an excellent antitumor therapeutic efficacy in both primary and metastatic tumors as compared to the relatively hydrophobic ones. Further analyses revealed that the superior antitumor outcome was attributed to the balance of tumor accumulation and cellular uptake, demonstrating the particular importance of nanoparticle surface hydrophilicity regulation on the antitumor efficacy. Our work provides a potent guideline for a rational designation on the surface hydrophilicity of nanoparticles for cancer treatment optimization.
Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Sistemas de Liberação de Medicamentos , Melanoma Experimental/tratamento farmacológico , Nanomedicina , Nanopartículas/química , Polifosfatos/química , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Docetaxel/química , Ensaios de Seleção de Medicamentos Antitumorais , Interações Hidrofóbicas e Hidrofílicas , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Tamanho da Partícula , Polifosfatos/síntese química , Propriedades de SuperfícieRESUMO
Aiming at development of a micellar nanoparticle system for intracellular drug release triggered by glutathione in tumor cells, a disulfide-linked biodegradable diblock copolymer of poly(epsilon-caprolactone) and poly(ethyl ethylene phosphate) was synthesized. It formed biocompatible micelles loaded with doxorubicin in aqueous solution but detached the shell material under glutathione stimulus, resulting in rapid drug release with destruction of micellar structure. These glutathione-sensitive micelles also rapidly released the drug molecules intracellularly and led to enhanced growth inhibition to A549 tumor cells, suggesting that this nanoparticle system may have potential for improving drug delivery efficacy.
Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Espaço Intracelular/metabolismo , Micelas , Fosfatos/química , Poliésteres/química , Transporte Biológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , HumanosRESUMO
Novel thermoresponsive block copolymers of poly(ethylene glycol) and polyphosphoester were synthesized, and the thermo-induced self-assembly, biocompatibility, and hydrolytic degradation behavior were studied. The block copolymers with various molecular weights and compositions were synthesized through ring-opening polymerization of 2-ethoxy-2-oxo-1,3,2-dioxaphospholane (EEP) and 2-isopropoxy-2-oxo-1,3,2-dioxaphospholane (PEP) using poly(ethylene glycol) monomethyl ether (mPEG) as the initiator and stannous octoate as the catalyst. The obtained block polymers exhibited thermo-induced self-assembly behavior, demonstrated by dynamic light scattering and UV-vis measurements using 1,6-diphenyl-1,3,5-hexatriene as the probe. It was found that the critical aggregation temperature (CAT) of the block copolymers shifted to higher temperature with increased molecular weight of mPEG, while copolymerization with more hydrophobic monomer PEP led to lower transition temperature; thus, the CAT can be conveniently adjusted. The block copolymers did not induce significant hemolysis and plasma protein precipitation. In vitro MTT and live/dead staining assays indicated they are biocompatible, and the biocompatibility was further demonstrated in vivo by the absence of local acute inflammatory response in mouse muscle following intramuscular injection. Unlike most frequently studied thermoresponsive poly(N-isopropylacrylamide), polyphosphoesters were hydrolytically degradable in aqueous solution that was proven by gel permeation chromatography and NMR analyses, and the degradation products were proven to be nontoxic to HEK293 cells. Therefore, with good biocompatibility and thermoresponsiveness, these biodegradable block copolymers of mPEG and polyphosphoesters are promising as stimuli-responsive materials for biomedical applications.
Assuntos
Materiais Biocompatíveis/química , Poliésteres/química , Polietilenoglicóis/química , Polifosfatos/química , Temperatura , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologia , Coleta de Amostras Sanguíneas , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Hemólise/efeitos dos fármacos , Hemólise/fisiologia , Humanos , Hidrólise , Espectroscopia de Ressonância Magnética , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Peso Molecular , Poliésteres/farmacologia , Polietilenoglicóis/farmacologia , Polifosfatos/farmacologia , Fatores de TempoRESUMO
Surface modification is often needed in tissue engineering to enhance the interaction between cells and synthetic materials and improve the cytocompatibility and cellular functions. In this study, block copolymers of poly(L-lactic acid) and poly(ethyl ethylene phosphate) (PLLA-b-PEEP) were synthesized and used to modify the PLLA surface via a spin-coating process, to understand whether surface modification with polyphosphoester-based polymer will be osteoinductive for potential bone tissue engineering applications. X-ray photoelectron spectra measurements revealed that phosphorus atomic compositions after surface modification increased from 2.09% to 4.39% with increasing PEEP length of PLLA-b-PEEP from 58 to 224 units, which also led to a more hydrophilic surface property compared with unmodified PLLA. The initial osteoblast attachment and proliferation on the modified surfaces were significantly enhanced. Moreover, cellular alkaline phosphatase activity and mineral calcium depositions were also promoted by PEEP modification. The gene expression determined by reverse transcription polymerase chain reaction further revealed that type I collagen and osteocalcin expression were upregulated in osteoblasts cultured on the modified surfaces, indicating that PEEP modification might be potentially osteoinductive and favorable for further application in bone tissue engineering.
Assuntos
Materiais Biocompatíveis/química , Proliferação de Células , Ésteres/química , Osteoblastos/citologia , Osteoblastos/metabolismo , Polímeros/química , Fosfatase Alcalina/metabolismo , Animais , Animais Recém-Nascidos , Materiais Biocompatíveis/síntese química , Cálcio/metabolismo , Adesão Celular , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Polímeros/síntese química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Engenharia TecidualRESUMO
Ridge-furrow with full film mulching (RFFM) is widely used in the Loess Plateau (LP) to increase maize yield. However, continuous RFFM application may cause excessive depletion of soil organic carbon (SOC) and soil water storage (SWS). The present study tested four production systems, namely, (1) RFFM; (2) ridge-furrow with polyethylene film and straw mulching (RFFSM); (3) non-contoured seedbed with film mulching (FFM); and (4) non-contoured seedbed without mulching (CK) in 2013 and 2014 to identify an optimal technique to increase maize yield yet minimizing the negative effects. SWS under RFFSM was significantly higher by 5.4% and 13.4% compared to RFFM and CK, respectively. The changes in SOC were -0.2, -0.2, and -0.4 g·kg-1 for RFFM, FFM, and CK, respectively, and 0.3 g·kg-1 for RFFSM. Increased root residue and extra external carbon input to soil under RFFSM directly contributed to SOC recovery. RFFSM had a comparable grain yield but higher water use efficiency compared to RFFM. The combination of RFFSM is promising for improving SOC stocks, water storage, and maize productivity.
Assuntos
Agricultura/métodos , Carbono/análise , Solo/química , Água/análise , Zea mays/crescimento & desenvolvimento , China , PolietilenoRESUMO
Gentiana apiata N. E. Brown (Gentianaceae) is a perennial herb plant and only grows in Qinba Mountains in China. Here, we first characterized the complete nucleotide sequence of chloroplast (cp) genome of G. apiata via Illumina next generation sequencing platform. The complete chloroplast genome of G. apiata was 144,274 bp in length, comprising of a large single copy (LSC) region of 77,353 bp, a small single copy (SSC) region of 17,009 bp, and two inverted repeat regions (IRs) of 24,956 bp. The cp genome contains 127 genes, including 82 protein-coding genes, 35 tRNA, eight rRNA genes, and two pseudogenes. Phylogenetic analysis based on 18 cp genome sequences showed that G. apiata closely related to congeneric species.
RESUMO
The tumor hypoxic microenvironment (THME) has a profound impact on tumor progression, and modulation of the THME has become an essential strategy to promote photodynamic therapy (PDT). Here, an oxygen self-supplied nanodelivery system that is based on nanometal-organic frameworks (nMOFs) with embedded AuNPs (Au@ZIF-8) on the nMOF surface as a catalase (CAT)-like nanozyme and encapsulating Ce6 inside as a photosensitizer was found to mitigate tumor hypoxia and reinforce PDT. As soon as Au@ZIF-8 reaches the tumor site, the AuNP nanozyme can catalyze excessive H2O2 to produce O2 to alleviate tumor hypoxia, promoting the production of 1O2 with strong toxicity toward tumor cells under irradiation. Our study demonstrates that nMOFs embellished with a nanozyme have great potential for overcoming the THME for cancer therapeutics, which provides a facile strategy for accurate bioimaging and cancer therapy in vivo.
Assuntos
Catalase/metabolismo , Portadores de Fármacos/química , Ouro/química , Nanopartículas Metálicas/química , Compostos Organometálicos/química , Fotoquimioterapia/métodos , Animais , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Clorofilídeos , Peróxido de Hidrogênio/metabolismo , Camundongos , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiaçãoRESUMO
A series of novel amphiphilic triblock copolymers of poly(ethyl ethylene phosphate) and poly(-caprolactone) (PEEP-PCL-PEEP) with various PEEP and PCL block lengths were synthesized and characterized. These triblock copolymers formed micelles composed of a hydrophobic core of poly(-caprolactone) (PCL) and a hydrophilic shell of poly(ethyl ethylene phosphate) (PEEP) in aqueous solution. The micelle morphology was spherical, determined by transmission electron microscopy. It was found that the size and critical micelle concentration values of the micelles depended on both hydrophobic PCL block length and PEEP hydrophilic block length. The in vitro degradation characteristics of the triblock copolymers were investigated in micellar form, showing that these copolymers were completely biodegradable under enzymatic catalysis of Pseudomonas lipase and phosphodiesterase I. These triblock copolymers were used for paclitaxel (PTX) encapsulation to demonstrate the potential in drug delivery. PTX was successfully loaded into the micelles, and the in vitro release profile was found to be correlative to the polymer composition. These biodegradable triblock copolymer micelles are potential as novel carriers for hydrophobic drug delivery.