RESUMO
Breast cancer remains a serious threat to women's physical and emotional health. The combination therapies can overcome the deficiency of single therapy, enhance the therapeutic effects and reduce the side effects at the same time. In this study, we synthesize a novel nanomedicine that enhanced the therapeutic effects of breast cancer treatment by combining photodynamic therapy and chemotherapy. The doxorubicin (DOX) and photosensitizer methyl pyropheophorbide-a (MPPa) are loaded into the nano-drug delivery system as DPSPFA/MPPa/DOX. In response to near-infrared (NIR) laser, the drugs were quickly released to the cancer cells. The MPPa produces reactive oxygen species (ROS) under the action of photodynamics. Unsaturated fatty acids with ROS promotes lipid peroxidation and the combination of chemotherapy and photodynamic therapy. The data shows that the DPSPFA/MPPa/DOX has a spherical shape, good dispersibility and stability, and the particle size is roughly 200â¯nm. The drug loading capability of DOX is about 13â¯%. Both of MCF7 cell model in vitro and breast cancer model in vivo, DPSPFA/MPPa/DOX showed an excellent anti-tumor effect of 86.9â¯% and without any obvious side effects. These findings might offer potential for a new approach for breast cancer treatment.
Assuntos
Neoplasias da Mama , Ácidos Docosa-Hexaenoicos , Doxorrubicina , Peroxidação de Lipídeos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/química , Células MCF-7 , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Animais , Ácidos Docosa-Hexaenoicos/química , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/síntese química , Camundongos , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Sobrevivência Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , PorfirinasRESUMO
Neuronal damage caused by oxidative stress and inflammatory microenvironment dominated by microglia are the main obstacles in the treatment of Parkinson's disease (PD). In this study, we developed an integrated nanoreactor Q@CeBG by encapsulating CeO2 nanozyme and quercetin (Que) into glutathione-modified bovine serum albumin, and then selected focused ultrasound (FUS) to temporarily open the blood-brain barrier (BBB) to enhance the accumulation level of Q@CeBG in the brain. Q@CeBG exhibited superior multi-ROS scavenging activity. Under the assistance of FUS, Q@CeBG nanoreactor can penetrate the BBB and act on neurons as well as microglia, reducing the neuron's oxidative stress level and polarizing microglia's phenotype from proinflammatory M1 to anti-inflammatory M2. In vitro and In vivo experiments demonstrated that Q@CeBG nanoreactor with good biocompatibility exhibit outstanding neuroprotection and immunomodulatory effects. In short, this dual synergetic nanoreactor will become a reliable platform against PD.
Assuntos
Microglia , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Espécies Reativas de Oxigênio , Encéfalo , NanotecnologiaRESUMO
Ischemic stroke is a neurological disease that leads to brain damage and severe cognitive impairment. In this study, extracellular vesicles(Ev) derived from mouse hippocampal cells (HT22) were used as carriers, and adenosine (Ad) was encapsulated to construct Ev-Ad to target the damaged hippocampus. The results showed that, Ev-Ad had significant antioxidant effect and inhibited apoptosis. In vivo, Ev-Ad reduced cell death and reversed inflammation in hippocampus of ischemic mice, and improved long-term memory and learning impairment by regulating the expression of the A1 receptor and the A2A receptor in the CA1 region. Thus, the developmental approach based on natural carriers that encapsulating Ad not only successfully restored nerves after ischemic stroke, but also improved cognitive impairment in the later stage of ischemic stroke convalescence. The development and design of therapeutic drugs provides a new concept and method for the treatment of cognitive impairment in the convalescent phase after ischemic stroke.
Assuntos
Vesículas Extracelulares , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Camundongos , Adenosina/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Hipocampo , Vesículas Extracelulares/metabolismo , Cognição , AVC Isquêmico/metabolismoRESUMO
Collagen, as the main component of human skin, plays a vital role in maintaining dermal integrity. Its loss will lead to dermis destruction and collapse, resulting in skin aging. At present, injection of exogenous collagen is an important means to delay skin aging. In this study, high-purity collagen was extracted from porcine skin. Our research revealed that it can effectively promote the adhesion and chemotaxis of HSF cells. It can also reduce the expression of ß-galactosidase, decrease ROS levels, and increase the expression of the collagen precursors, p53 and p16 in HSF cells during senescence. After local injection into the aging skin of rats, it was found that the number of cells and type I collagen fibers in the dermis increased significantly, and the arrangement of these fibers became more uniform and orderly. Moreover, the important thing is that it is biocompatible. To sum up, the porcine skin collagen we extracted is an anti-aging biomaterial with application potential.
Assuntos
Envelhecimento da Pele , Suínos , Humanos , Ratos , Animais , Derme/metabolismo , Quimiotaxia , Pele/metabolismo , Colágeno/metabolismo , Fibroblastos , Células CultivadasRESUMO
Oral ulcer is a common inflammatory disease of oral mucosa, causing severe burning pain and great inconvenience to daily life. In this study, compound 3J with anti-inflammatory activity was synthesized beforehand. Following that, an intelligent composite hydrogel supported 3J was designed with sodium alginate, carboxymethyl chitosan, and chitosan quaternary ammonium salt as the skeleton, and its therapeutic effect on the rat oral ulcer model was investigated. The results show that the composite hydrogel has a dense honeycomb structure, which is conducive to drug loading and wound ventilation, and has biodegradability. It has certain antibacterial effects and good anti-inflammatory activity. When loaded with 3J, it reduced levels of TNF-α and IL-6 in inflammatory cells by up to 50.0%. It has excellent swelling and water retention properties, with a swelling rate of up to 765.0% in a pH 8.5 environment. The existence of a large number of quaternary ammonium groups, carboxyl groups, and hydroxyl groups makes it show obvious differences in swelling in different pH environments, which proves that it has double pH sensitivity. It is beneficial to adapt to the highly dynamic changes of the oral environment. Compared with single hydrogel or drug treatment, the drug-loaded hydrogel has a better effect on the treatment of oral ulcers.
RESUMO
The blood-brain barrier (BBB) is a major limiting factor that prevents the treatment of Parkinson's disease (PD). In the present study, MgOp@PPLP nanoparticles are explored by using MgO nanoparticles as a substrate, polydopamine as a shell, wrapping anti-SNCA plasmid inside, and modifying polyethylene glycol, lactoferrin, and puerarin on the surface to improve the hydrophilicity, brain targeting and antioxidant properties of the particles, respectively. MgOp@PPLP exhibits superior near-infrared radiation (NIR) response. Under the guidance of photothermal effect, these MgOp@PPLP particles are capable of penetrating the BBB and be taken up by neuronal cells to exert gene therapy and antioxidant therapy. In both in vivo and in vitro models of PD, MgOp@PPLP exhibits good neuroprotective effects. Therefore, combined with noninvasive NIR radiation, MgOp@PPLP nanoplatform with good biocompatibility becomes an ideal material to combat neurodegenerative diseases.
Assuntos
Barreira Hematoencefálica , Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológicoRESUMO
The use of intelligent insulin delivery systems has become more important for treating diabetes. In this study, a dual-responsive oral insulin delivery nanocarrier that responds to glucose and pH has been developed. First, the oleic acid hydrophobic modified guar gum (GG) was synthesized by the esterification reaction, and the γ-polyglutamic acid (γ-PGA) was coupled with GG by the amidation reaction. The obtained pH-responsive copolymer (γ-PGA-GG) was cross-linked by concanavalin A to obtain pH/glucose dual-responsive nanocarriers, and insulin was effectively loaded into the dual-responsive nanocarriers. The insulin-loaded nanoparticles can achieve effective pH and glucose responses, releasing insulin on demand. In vitro and in vivo studies demonstrated the dual-responsive nanoparticles can protect insulin against the pH changes in the digestive tract and deliver insulin into the body to exert a hypoglycemic effect. Moreover, the dual-responsive nanoparticles have significant potential to be employed for oral insulin delivery.
Assuntos
Insulina , Nanopartículas , Insulina/química , Nanopartículas/química , Gomas Vegetais , Administração Oral , Glucose , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Portadores de Fármacos/químicaRESUMO
Breast cancer has consistently had the highest incidence among women in the world. Tumor cell-derived extracellular vesicles (EV) have been leveraged as drug carriers for cancer treatment. Herein, we developed an efficient theranostic platform for breast cancer-specific delivery of lipophilic triphenylphosphonium (TPP)-modified therapeutic recombinant P53 proteins (TPP/P53) by breast cancer cell-derived EVs. We observed that the EVs were routinely captured by their patent cells, so when, TPP/P53 was loaded into the EVs (TPP/P53@EVs), TPP/P53 was targeted to the mitochondria of breast cancer cells, where it caused signal amplification and induced the death of breast cancer cells. Our findings demonstrated that the TPP/P53@EVs showed good tumor-targeting capability and efficiently destroyed the tumor tissues without any obvious toxicity in vivo. Therefore, our TPP/P53@EVs might provide a "drug-free" strategy for future applications in breast cancer therapy.
Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Portadores de Fármacos/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Humanos , Mitocôndrias/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Parkinson's disease (PD) always causes dyskinesia and cognitive impairments. The alpha-synuclein (α-syn) accumulation, one of the main pathological characteristics of PD, may impair synaptic structural and synaptic functions. Nano-MgO composites has been reported to interfere α-syn expression. The present study is aim to investigate the roles of nano-MgO composites on cognitive impairments in PD rats. PD rats were formed by 6-hydroxydopamine (6-OH DA) and α-syn expression were evaluated by Western blot. Hippocampal dendritic morphology was examined by Golgi staining. Morris water maze (MWM) test was applied to evaluate learning and memory abilities and population spike was recorded by electrophysiological records in vivo. The results showed that: 6-OH DA-treated up-regulated α-syn levels in striatum and hippocampus and increased the rotational times by APO, but nano-MgO composites could down-regulated α-syn levels. The overall length of dendritic and the total number of intersections were reduced by 6-OH DA, accompanied by the decrease of the dendritic spine density in hippocampal CA1, CA3 and DG regions. Interestingly, nano-MgO composites could alleviate the morphological damages of dendrites. In the MWM test, the escape latencies and the swimming distances in PD rats were increased as compared to the sham group, and nano-MgO composites could reduce the escapes latencies and the swimming distances. Furthermore, 6-OH DA reduced the amplitudes of long-term potentiation (LTP) in hippocampal CA1 region, and 6 mg/kg nano-MgO composites could improve LTP amplitudes. In conclusion, the current findings would be helpful to explore the roles of nano-MgO composites on neuroprotection in PD.
Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Animais , DNA , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxidopamina , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Plasmídeos , Ratos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
Compared with injection, oral drug delivery is a better mode of administration because of its security, low pain and simplicity. Insulin is the first choice for clinical treatment of type 1 diabetes, but, because insulin inability to resist gastrointestinal (GI) digestion results in poor oral bioavailability of insulin. Herein, we developed a targeted oral delivery system for diabetes. ConA-INS-KGM nanoparticles were prepared, loaded with insulin, fabricated from konjac glucomannan (KGM) and concanavalin A (ConA) through a crosslinking method, as an insulin oral delivery system in response to different blood glucose levels. The size of nanoparticles was characterized by TEM, which showed that these nanoparticles were formed spherical particles with a diameter of about 500 nm. In vitro release of insulin from these nanoparticles was studied, which indicated that insulin release is reversible at different glucose concentrations. In vivo tests demonstrated that they are safe and have high biocompatibility. Using the nanoparticles to treat diabetic mice, we found that they can control blood sugar levels for 6 h, retaining their glucose-sensitive properties during this time. Therefore, these nanoparticles have significant potential as glucose-responsive systems for diabetes and show great applications in biomedical fields.
Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Administração Oral , Animais , Glicemia , Concanavalina A , Diabetes Mellitus Experimental/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Glucose , Insulina , Mananas , CamundongosRESUMO
In this research, resveratrol (RSV)-loaded scaffolds have been prepared to control the release of resveratrol and used to delay hepatic stellate cell (HSC) senescence in vitro. The functional carboxyl group-COOH is first introduced to the surface of poly(ε-caprolactone/d,l-lactide) (P(CL-DLLA)) under the coadministration of ultra-violet (UV) treatment and photo initiator and then resveratrol are conjugated onto the surface of the modified scaffolds through esterification. The characterization of the structure of RSV-AA-P(CL-DLLA) shows that resveratrol has been successfully conjugated onto the modified surface. Cell growth exhibits a higher level of cell viability and much more obvious agglomeration on the surface of the synthetic RSV-AA-P(CL-DLLA). Meanwhile the activity of senescence-associated ß-galactosidase (SA-ß-gal) and reactive oxygen species (ROS) is downgulated for cells on RSV-AA-P(CL-DLLA), which suggests that cell senescence is delayed on RSV-AA-P(CL-DLLA). And then it is attested that cells have a lower level of p53 but SIRT1 expression is upregulated on RSV-AA-P(CL-DLLA), which might be related to resveratrol release from RSV-AA-P(CL-DLLA). It also suggested cell senescence on RSV-AA-P(CL-DLLA) has been regulated by p53 and the SIRT1 signaling pathway. In all, the present study shows that RSV-AA-P(CL-DLLA) can be successfully prepared to promote cell growth and delay cell senescence and could be used for cell-based therapy in tissue engineering.
Assuntos
Sirtuína 1 , Proteína Supressora de Tumor p53 , Sobrevivência Celular , Senescência Celular , Resveratrol/farmacologiaRESUMO
Breast cancer is one of the most common cancers in the world with tumor heterogeneity. Currently, cancer treatment mainly relies on surgical intervention, chemotherapy, and radiotherapy, for which the side effects, drug resistance and cost need to be resolved. In this study, we develop a natural medicine targeted therapy system. Phosphatidylcholine (PC), doxorubicin (DOX), procyanidin (PA), and epigallocatechin gallate (EGCG) are assembled and PC@DOX-PA/EGCG nanoparticles (NPs) are obtained. In addition, the HER2, ER and PR ligands were grafted on the surface of the NPs to acquire the targeted nanoparticles NP-ER, NP-ER-HER2, and NP-ER-HER2-PR. The physicochemical properties of the nanoparticles were detected and it was found that the nanoparticles are spherical and less than 200 nm in diameter. Furthermore, in vitro and in vivo results indicate that the nanoparticles can target BT-474, MCF-7, EMT-6, and MDA-MB-231 breast cancer cells, effectively inhibiting the growth of the breast cancer cells. In short, this research will provide some strategies for the treatment of heterogeneous breast cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Micelas , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Biflavonoides/química , Catequina/análogos & derivados , Catequina/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Humanos , Ligantes , Camundongos Endogâmicos BALB C , Fosfatidilcolinas/química , Proantocianidinas/químicaRESUMO
Although gene therapy targeting the α-synuclein gene (SNCA) has achieved outstanding results in the treatment of Parkinson's disease (PD), the lack of a suitable gene delivery system and inadequate therapeutic effects remains a tremendous obstacle for RNAi therapy. Here, a degradable nano-MgO micelle composite (MgO(pDNA)-INS-Plu-mRNA-NGF) with double interference (mediated by RNAi and α-synuclein (α-syn)-targeted mRNA) was constructed. Binding mRNA treatment significantly increased the inhibitory effect compared to the reduction of α-syn expression by RNAi alone. Moreover, the cell experiments demonstrated that the viability of the PD cell model can be significantly improved by nano-MgO micelle composite treatment. More importantly, the composite has the ability to penetrate the blood brain barrier and deliver genes and mRNA to neurons through endocytosis mediated by the nerve growth factor and its receptors, thus significantly downregulating the expression of α-syn in the PD mice model without causing damage to other major organs. Overall, this work provides a novel insight into the design of biomaterials for gene therapy for PD.
Assuntos
Doença de Parkinson , Animais , Camundongos , Micelas , Neurônios/metabolismo , Doença de Parkinson/terapia , Interferência de RNA , alfa-Sinucleína/genéticaRESUMO
Cell culturing on different synthetic biomaterials would reprogram cell metabolism for adaption to their living conditions because such alterations in cell metabolism were necessary for cellular functions on them. Here we used metabolomics to uncover metabolic changes when liver cells were cultured on insulin-like growth factor (IGF)/tumor necrosis factor-α (TNF-α) and chargeable polymers co-modified biomaterials with the aim to explain their modulating effects on cell metabolism. The results showed that cell metabolism on IGF-1/TNF-α co-immobilized conjugates was significantly regulated according to their scatterings on the score plot of principal component analysis. Specifically, cell metabolisms were reprogrammed to the higher level of pyrimidine metabolism, ß-alanine metabolism, and pantothenate and CoA biosynthesis, and the lower level of methionine salvage pathway in order to promote cell growth on IGF/TNF-α co-modified surface. Furthermore, cell senescence on PSt-PAAm-IGF/TNF-α surface was delayed through the regulation of branch amino acid metabolism and AMPK signal pathway. The research showed that metabolomics had great potential to uncover the molecular interaction between biomaterials and seeded cells, and provide the insights about cell metabolic reprogramming on IGF/TNF-α co-modified conjugates for cell growth.
Assuntos
Proliferação de Células , Fator de Crescimento Insulin-Like I , Polímeros , Transdução de Sinais , Fator de Necrose Tumoral alfa , Células Hep G2 , Humanos , Fator de Crescimento Insulin-Like I/química , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Polímeros/química , Polímeros/farmacologia , Fator de Necrose Tumoral alfa/química , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Bone diseases such as osteomalacia, osteoporosis, and osteomyelitis are major illnesses that threaten the health of human. This study aimed to provide an idea at the molecular level of material properties determined with UV specific surface approaches. The tert-butyl hydroperoxide (t-BHP) exposure aging model bone mesenchymal stem cells (BMSCs) were reverted by using a poly-hybrid scaffold (PS), which is a carbon nanotube (CNT) coated polycaprolactone (PCL) and polylactic acid (PLA) scaffold, combined with insulin-like growth factor-1 (IGF). Then, the region-specific PS photo-immobilized with different growth factors (GFs) was obtained by interference and diffraction of ultraviolet (UV) light. Additionally, the reverted BMSCs were regionally pattern differentiated into three kinds of cells on the GF immobilized PS (GFs/PS). In vivo, the GFs/PS accelerate bone healing in injured Sprague-Dawley (SD) rats. The data showed that GFs/PS effectively promoted the differentiation of reverted BMSCs in the designated area on 21st day. These results suggest region-specific interface immobilization of GFs concurrently differentiating reverted BMSCs into three different cells in the same scaffold. This method might be considered as a short-time, low cost, and simple operational approach to scaffold modification for tissue regeneration in the future.
Assuntos
Células da Medula Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Células Imobilizadas/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Alicerces Teciduais , Raios Ultravioleta , Animais , Células da Medula Óssea/fisiologia , Células da Medula Óssea/efeitos da radiação , Regeneração Óssea/fisiologia , Regeneração Óssea/efeitos da radiação , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Diferenciação Celular/efeitos da radiação , Células Cultivadas , Células Imobilizadas/fisiologia , Células Imobilizadas/efeitos da radiação , Feminino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Mesenquimais/efeitos da radiação , Ratos , Ratos Sprague-DawleyRESUMO
Parkinson's disease (PD) is characterized by motor and non-motor symptoms, primarily affecting dopaminergic neurons (DAergic neurons) in substantia nigra (SN). However, it is still very challenging to identify new drugs that not only inhibit motor dysfunction but also improve non-motor dysfunction. It has been identified as a potential PD treatment that the inhibition of α-syn aggregation could decrease the death of DAergic neurons in SN. In this study, we synthesized gold nanoparticle composites (NPs) that were loaded with plasmid DNA (pDNA) to inhibit α-syn expression. In vivo, our results showed that NPs improved tyrosine hydroxylase (TH) levels and decreased aggregation of α-syn in the SN. Additionally, NPs attenuated motor dysfunction and exploration ability declined. Moreover, NPs reversed the inhibition of long-term potentiation (LTP) and improved non-motor dysfunction in PD mice. These results indicated that NPs had significantly neuroprotective effects not only in motor, but also in non-motor dysfunction to PD mice, providing a new strategy for gene therapy in PD.
Assuntos
Disfunção Cognitiva , Nanopartículas Metálicas , Doença de Parkinson , Animais , Modelos Animais de Doenças , Ouro , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/tratamento farmacológico , Substância NegraRESUMO
The use of bone tissue engineering scaffolds has become a promising potential treatment for bone defects as they expedite bone healing. A carbon nanotube-hydroxyapatite (CNT-HA) composite can accelerate the growth of cells. However, the molecular organized arrangement of organic and inorganic components is one of the most important biochemical phenomena in the formation of bones. This study aimed to prepare ordered CNT-HA scaffolds by applying agarose gel electrophoresis to imitate a biomimetic parallel pattern of collagens and hydroxyapatite hydrogel scaffolds (AG-Col-o-CNT). Significant improvements were presented in the mechanical properties of the scaffolds and cell growth in vitro or in vivo. The results showed that the AG-Col-o-CNT scaffolds accelerated the proliferation and differentiation of bone mesenchymal stem cell lines. In addition, the bone defects were repaired when the scaffolds were transplanted after 28 and 56 days in vivo. The superior performance of the ordered AG-Col-o-CNT scaffolds indicates that they have an enormous potential for bone tissue engineering.
Assuntos
Materiais Biomiméticos/química , Durapatita/química , Hidrogéis/química , Nanotubos de Carbono/química , Engenharia Tecidual , Alicerces Teciduais/química , Animais , Materiais Biomiméticos/farmacologia , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Durapatita/farmacologia , Hidrogéis/farmacologia , Teste de Materiais , Células-Tronco Mesenquimais/efeitos dos fármacos , RatosRESUMO
Lung is one of important organs and lung diseases seriously affect the health of human beings. In this study, chitosan and gelatin as natural biological macromolecules raw material for the synthesis of ordered colloidal crystal scaffolds (CCS), Fe3O4 magnetic nanoparticles (MNPs) were used as pore-making for the first time. The pore-making agent were added into the hydrogels to synthesis the ordered (magnetic field) and disordered (no magnetic field) CCS. Collagen and basic fibroblast growth factor (bFGF) modified on the surface of CCS. Then mouse lung epithelial cells (TC-1) and normal human bronchial epithelial cells (Beas-2B) were cultured on the scaffold, obviously induced cell proliferation. Various physical and chemical characteristics indicate that the preparation of scaffolds and modified growth factors can greatly promote the proliferation of these two cells. In addition, the scafolld was implanted into the SD rat in vivo, and routine blood tests showed that the stent had a small inflammatory response to the rat. This may be one of the effective strategies for the future treatment of lung injury repair.
Assuntos
Coloides/química , Células Epiteliais/citologia , Pulmão/citologia , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis , Brônquios/citologia , Proliferação de Células , Células Cultivadas , Quitosana/química , Colágeno/química , Cristalização , Feminino , Gelatina/química , Humanos , Inflamação , Teste de Materiais , Camundongos , Nanopartículas/química , Porosidade , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Temperatura , Engenharia Tecidual/métodosRESUMO
Using external methods to induce the death of cancer cells is recognized as one of the main strategies for cancer treatment. Research indicated that TNF-α is frequently used in tumor biotherapy while IFN-γ can directly inhibit tumor cell proliferation. In our study, TNF-α and IFN-γ were coimmobilized on polystyrene material (PSt) or Fe3O4-oleic acid nanoparticles (NPs). Then the structural change of these two proteins can be observed. Meanwhile, the expressions of both TNF-α and IFN-α increased significantly, as determined by gene microarray analysis; however, in the presence of TNF-α plus IFN-α inhibitors, TNF-α and IFN-α did not increase in HeLa cells induced by coimmobilized IFN-γ plus TNF-α. Our results indicate that such change can stimilate HeLa cells to secrete more TNF-α and IFN-α, by which the apoptosis of HeLa cells could be further induced. This study is the first report of autocrine-induced apoptosis of HeLa cells. In addition, we performed ELISA, RT-PCR, flow cytometry, and Western blot analyses, as well as a series of analytical tests at the animal level. our data also indicate that the PSt-coimmobilized IFN-γ plus TNF-α has apparent effects for cancer treatment in vivo, which is of great significance for translation into clinical medicine.
Assuntos
Apoptose , Animais , Comunicação Autócrina , Materiais Biocompatíveis , Feminino , Células HeLa , Humanos , Interferon gama , Fator de Necrose Tumoral alfa , Neoplasias do Colo do ÚteroRESUMO
Parkinson's disease (PD) is second most common neurodegenerative disorder worldwide. Although drugs and surgery can relieve the symptoms of PD, these therapies are incapable of fundamentally treating the disease. For PD patients, over-expression of α-synuclein (SNCA) leads to the death of dopaminergic neurons. This process can be prevented by suppressing SNCA over-expression through RNA interference. Here, we successfully synthesized gold nanoparticles (GNP) composites (CTS@GNP-pDNA-NGF) via the combination of electrostatic adsorption and photochemical immobilization, which could load plasmid DNA (pDNA) and target specific cell types. GNP was transfected into cells via endocytosis to inhibiting the apoptosis of PC12 cells and dopaminergic neurons. Simultaneously, GNP composites are also used in PD models in vivo, and it can successfully cross the blood-brain barrier by contents of GNP in the mice brain. In general, all the works demonstrated that GNP composites have good therapeutic effects for PD models in vitro and in vivo.