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1.
J Nanobiotechnology ; 21(1): 129, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37055835

RESUMO

BACKGROUND: Excessive oxidative stress at the wound sites always leads to a prolonged healing and even causes chronic inflammatory wounds. Therefore, antioxidative dressings with multiple features are desired to improve wound healing performance. Herein, we fabricated a ROS-scavenging hybrid hydrogel by incorporating mussel-inspired fullerene nanocomposites (C60@PDA) into gelatin methacryloyl (GelMA) hydrogel. RESULTS: The developed C60@PDA/GelMA hydrogel showed a sustainable free radical scavenging ability, and eliminated ROS to protect cells against external oxidative stress damage. Besides, the hydrogel presented favorable cytocompatibility, hemocompatibility, and antibacterial ability in vitro. Furthermore, in a mouse full-thickness wound defect model, the in situ forming hybrid hydrogel accelerated wound closure by 38.5% and 42.9% on day 3 and day 7 over the control. Histological results demonstrated that hybrid hydrogels effectively enhanced wound healing on re-epithelialization, collagen deposition and angiogenesis. CONCLUSION: Collectively, the C60@PDA/GelMA hydrogel could be a promising dressing for promoting cutaneous wound repair.


Assuntos
Fulerenos , Nanocompostos , Animais , Camundongos , Hidrogéis , Cicatrização , Fulerenos/farmacologia , Espécies Reativas de Oxigênio , Modelos Animais de Doenças , Nanocompostos/uso terapêutico , Antibacterianos/farmacologia
2.
J Nanobiotechnology ; 21(1): 435, 2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-37981675

RESUMO

BACKGROUND: Bacterial infection, complex wound microenvironment and persistent inflammation cause delayed wound healing and scar formation, thereby disrupting the normal function and appearance of skin tissue, which is one of the most problematic clinical issues. Although Ag NPs have a strong antibacterial effect, they tend to oxidize and form aggregates in aqueous solution, which reduces their antibacterial efficacy and increases their toxicity to tissues and organs. Current research on scar treatment is limited and mainly relies on growth factors and drugs to reduce inflammation and scar tissue formation. Therefore, there is a need to develop methods that effectively combine drug delivery, antimicrobial and anti-inflammatory agents to modulate the wound microenvironment, promote wound healing, and prevent skin scarring. RESULTS: Herein, we developed an innovative Ag nanocomposite hydrogel (Ag NCH) by incorporating Ag nanoparticles (Ag NPs) into a matrix formed by linking catechol-modified hyaluronic acid (HA-CA) with 4-arm PEG-SH. The Ag NPs serve dual functions: they act as reservoirs for releasing Ag/Ag+ at the wound site to combat bacterial infections, and they also function as cross-linkers to ensure the sustained release of basic fibroblast growth factor (bFGF). The potent antibacterial effect of the Ag NPs embedded in the hydrogel against S.aureus was validated through comprehensive in vitro and in vivo analyses. The microstructural analysis of the hydrogels and the in vitro release studies confirmed that the Ag NCH possesses smaller pore sizes and facilitates a slower, more sustained release of bFGF. When applied to acute and infected wound sites, the Ag NCH demonstrated remarkable capabilities in reshaping the immune and regenerative microenvironment. It induced a shift from M1 to M2 macrophage polarization, down-regulated the expression of pro-inflammatory factors such as IL-6 and TNF-α, and up-regulated the expression of anti-inflammatory IL-10. Furthermore, the Ag NCH played a crucial role in regulating collagen deposition and alignment, promoting the formation of mature blood vessels, and significantly enhancing tissue reconstruction and scarless wound healing processes. CONCLUSIONS: We think the designed Ag NCH can provide a promising therapeutic strategy for clinical applications in scarless wound healing and antibacterial therapy.


Assuntos
Cicatriz , Nanopartículas Metálicas , Humanos , Antibacterianos/farmacologia , Preparações de Ação Retardada , Inflamação , Nanogéis , Prata/farmacologia , Cicatrização , Nanocompostos
3.
Small ; 16(32): e2000796, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32633072

RESUMO

Piezoelectric materials can produce electrical power from the mechanical stimulation and thus, they may accelerate electroactive tissue healing as a promising treatment for traumatic peripheral nerve injuries. In this study, a piezoelectric zinc oxide nanogenerator scaffold is manufactured by 3D injectable multilayer biofabrication. The piezoelectric polymeric scaffold displays desirable mechanical and physical characteristics, such as aligned porosity, high elasticity, scaffold stiffness, surface energy, and excellent shear behavior. In addition, its biocompatibility supplies Schwann cells with an adhesive, proliferative, and angiogenic interface, as is reflected by higher expression of functional proteins including nerve growth factor (NGF) and vascular endothelial growth factor (VEGF). In vivo mechanical stimuli by treadmill practice contribute to the comprehensive reparative therapy. The piezoelectric conduit accelerates nerve conducting velocity, promotes axonal remyelination, and restores motor function by recovering endplate muscles. Moreover, the piezoelectric nanogenerator scaffold creates biomimetic electrically conductive microenvironment without causing noticeable toxicity to functioning organs and improves peripheral nerve restoration by the multifunctional characteristics. Therefore, the mechano-informed biomimetic piezoelectric scaffold may have enormous potential in the neuroengineering for regenerative medicine.


Assuntos
Biomimética , Óxido de Zinco , Axônios , Polímeros , Alicerces Teciduais , Fator A de Crescimento do Endotélio Vascular
4.
J Nanobiotechnology ; 18(1): 46, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32169062

RESUMO

BACKGROUND: Peripheral nerve injury is one common clinical disease worldwide, in which sciatic nerve is anatomically the most challenging to regenerate given its length and large cross-sectional area. For the present, autologous nerve grafting remains to be the most ideal strategy when treating with sciatic nerve injury. However, this method sacrifices healthy nerves and requires highly intensive surgery, still calling for other advanced alternatives for nerve grafting. RESULTS: In this study, we utilized previously well-established gene delivery system to dually deliver plasmid DNA (pDNA) encoding vascular endothelial growth factor (VEGF) and nerve growth factor (NGF), exploring therapeutics for sciatic nerve injury. Low-molecular-weight branched polyethylenimine (bPEI) was constructed as the backbone structure of gene vectors, and it was further crosslinked to synthesize degradable polycations via the conjugation of dialdehydes. Potential synergistic effect between VEGF and NGF proteins were observed on rat sciatic nerve crush injury model in this study. CONCLUSIONS: We concluded that dual delivery of plasmid VEGF and NGF as gene therapy could enhance sciatic nerve regeneration.


Assuntos
Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Regeneração Nervosa/fisiologia , Nervo Isquiático/crescimento & desenvolvimento , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Anoplura/química , Autoenxertos , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Terapia Genética/métodos , Vetores Genéticos , Nanopartículas/química , Tamanho da Partícula , Polietilenoimina , Piridinas , Ratos , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Neuropatia Ciática
5.
Nano Lett ; 19(12): 8990-9001, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31790262

RESUMO

Black phosphorus is well known for its excellent electromechanical properties. Although it has previously been used for therapeutic drug delivery in cancer, it has never been applied as an electroactive polymer for post-trauma tissue regeneration (e.g., in cardiac muscles and neurons). The major concern currently preventing such applications is its controversial biosafety profile in vivo. Here, we demonstrate the production of a concentrically integrative layer-by-layer bioassembled black phosphorus nanoscaffold. This scaffold has remarkable electrical conductivity, permitting smooth release into the surrounding microenvironment. We confirmed that, under mild oxidative stress, our black phosphorus nanoscaffold induced angiogenesis and neurogenesis and stimulated calcium-dependent axon regrowth and remyelination. Long-term in vivo implantation of this nanoscaffold during severe neurological defect regeneration induced negligible toxicity levels. These results provide new insight into the regenerative capability of manufactured 3D scaffolds using neuroengineered 2D black phosphorus nanomaterials.


Assuntos
Homeostase/efeitos dos fármacos , Nanoestruturas/química , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Alicerces Teciduais/química , Células A549 , Animais , Células HeLa , Humanos , Células PC12 , Ratos , Ratos Sprague-Dawley
6.
Nanomedicine ; 17: 188-197, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30721753

RESUMO

Nontoxic and nonimmunogenic nanoparticles play an increasingly important role in the application of pharmaceutical nanocarriers. The pathogenesis of diabetic peripheral neuropathy (DPN) has been extensively studied. However, the role of microRNAs in DPN remains to be clarified. We verified in vitro that miR-146a-5p mimics inhibited the expression of proinflammatory cytokines and apoptosis. Then, we explored the protective effect of nanoparticle-miRNA-146a-5p polyplexes (nano-miR-146a-5p) on DPN rats. We demonstrated that nano-miR-146a-5p improved nerve conduction velocity and alleviated the morphological damage and demyelination of the sciatic nerve of DPN rats. The expression of the inflammatory cytokines, caspase-3, and cleaved caspase-3 in the sciatic nerve was inhibited by nano-miR-146a-5p. Additionally, nano-miR-146a-5p increased the expression of myelin basic protein. These results all indicated that nano-miR-146a-5p had a protective effect on peripheral nerves in the DPN rat model, which may occur through the regulation of the inflammatory response and apoptosis.


Assuntos
Apoptose , Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/terapia , Inflamação/terapia , MicroRNAs/uso terapêutico , Nanopartículas/uso terapêutico , Animais , Linhagem Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/genética , Neuropatias Diabéticas/patologia , Terapia Genética , Ratos , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
7.
J Pineal Res ; 65(4): e12516, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29935084

RESUMO

Peripheral nerve defect is a common and severe kind of injury in traumatic accidents. Melatonin can improve peripheral nerve recovery by inhibiting oxidative stress and inflammation after traumatic insults. In addition, it triggers autophagy pathways to increase regenerated nerve proliferation and to reduce apoptosis. In this study, we fabricated a melatonin-controlled-release scaffold to cure long-range nerve defects for the first time. 3D manufacture of melatonin/polycaprolactone nerve guide conduit increased Schwann cell proliferation and neural expression in vitro and promoted functional, electrophysiological and morphological nerve regeneration in vivo. Melatonin nerve guide conduit ameliorated immune milieu by reducing oxidative stress, inflammation and mitochondrial dysfunction. In addition, it activated autophagy to restore ideal microenvironment, to provide energy for nerves and to reduce nerve cell apoptosis, thus facilitating nerve debris clearance and neural proliferation. This innovative scaffold will have huge significance in the nerve engineering.


Assuntos
Autofagia/efeitos dos fármacos , Melatonina/farmacologia , Regeneração Nervosa/efeitos dos fármacos , Actinas/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Eletrofisiologia , Inflamação/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Melatonina/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Poliésteres/química , Ratos , Ratos Sprague-Dawley , Regeneração/efeitos dos fármacos , Células de Schwann , Alicerces Teciduais/química , Tubulina (Proteína)/metabolismo
8.
BMC Infect Dis ; 18(1): 543, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30382821

RESUMO

BACKGROUND: China had the third highest burden of tuberculosis population in the world. Bone and joint tuberculosis was a major part and its characteristics were rarely discussed before. This study was designed to review the characteristics and management of bone and joint tuberculosis among native and migrant population in Shanghai, China during 2011-2015. METHODS: A retrospective analysis of the patient clinical records on their demographic information, clinical features and treatment was conducted from three tertiary referral hospitals. Analysis of continuous variables included calculation of the median value with interquartile range. Categorical variables were displayed as percentages and compared using the Fisher's exact test and chi-square test. All continuous variables were compared using Student's unpaired t-test and Mann Whitney U test. RESULTS: One hundred fifteen patients with bone and joint tuberculosis were involved in this study. Native people were generally older (p = 0.003) and had more comorbidities like hypertension (40.74% vs. 16.39%, p = 0.004), diabetes mellitus (38.89% vs. 13.11%, p = 0.001), and cancer (31.48% vs. 14.75%, p = 0.032) than migrants. Migrant patients generally experienced a longer period of uncomfortable feelings before going to doctor than native people (p = 0.007). Spine was a major infection site in comparison with other peripheral joints. Radiological evaluation displayed increased osteolytic reaction in migrant patients compared with native people (p = 0.031). The mean time for anti-tuberculosis treatment was significantly longer in native Shanghai patients (8.96 months vs. 7.94 months, p = 0.003). The curative ratio displayed a significant difference between native and migrant patients (88.24%vs.75.93%, p = 0.009). CONCLUSION: Bone and joint tuberculosis exhibited a poorer outcome in migrant people, who also had longer period of manifestation, more severe osteolytic reaction from CT scan and higher recurrent rate than native people. The surgical treatment in addition to anti-tuberculosis drug therapy had great implications for bone and joint tuberculosis recovery.


Assuntos
Migrantes , Tuberculose Osteoarticular/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Tuberculose Osteoarticular/etnologia , Tuberculose Osteoarticular/terapia , População Urbana , Adulto Jovem
9.
J Nanobiotechnology ; 16(1): 74, 2018 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-30243297

RESUMO

With the improvement of nanotechnology and nanomaterials, redox-responsive delivery systems have been studied extensively in some critical areas, especially in the field of biomedicine. The system constructed by redox-responsive delivery can be much stable when in circulation. In addition, redox-responsive vectors can respond to the high intracellular level of glutathione and release the loaded cargoes rapidly, only if they reach the site of tumor tissue or targeted cells. Moreover, redox-responsive delivery systems are often applied to significantly improve drug concentrations in targeted cells, increase the therapeutic efficiency and reduce side effects or toxicity of primary drugs. In this review, we focused on the structures and types of current redox-responsive delivery systems and provided a comprehensive overview of relevant researches, in which the disulfide bond containing delivery systems are of the utmost discussion.


Assuntos
Antineoplásicos/administração & dosagem , Preparações de Ação Retardada/química , Dissulfetos/química , Neoplasias/tratamento farmacológico , Microambiente Tumoral , Animais , Antineoplásicos/farmacologia , Preparações de Ação Retardada/metabolismo , Dissulfetos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Glutationa/metabolismo , Humanos , Neoplasias/metabolismo , Oxirredução/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
10.
Nanomedicine ; 11(5): 1109-15, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25791814

RESUMO

Topical propranolol has been used for the therapy of superficial infantile hemangiomas (IH). A retrospective investigation was conducted in 50 patients to evaluate the clinical effect of a new type of topical nano-propranolol-dispersed hydrogel. Participants were treated 3 times per day for 2 weeks to 11 months. 68% of patients were female and 12% had received other treatments before therapy. The nano-propranolol 0.5% hydrogel was initiated at a mean age of 5.010 months and for a mean duration of 3.610 months. The response rate was 86%. No recurrence and rebound growth occurred after withdrawal of hydrogel. Slight side effects (application site itching, erosion and crusting) were observed in only 2 cases. All the local irritations were evaluated as mild and were tolerated without discontinuing the medication. We suggest that topical nano-propranolol hydrogel could be an alternative option for the treatment of uncomplicated superficial IH with satisfactory tolerability and optimal effectiveness. FROM THE CLINICAL EDITOR: The current recommended treatment for infantile hemangiomas is oral propranolol. Nonetheless, a small proportion of patients will have systemic side effects. In this article, the authors developed topical nano-propranolol hydrogel and tested this on clinical patients and found favorable response.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Hemangioma/tratamento farmacológico , Propranolol/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Pele/efeitos dos fármacos , Administração Tópica , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Feminino , Hemangioma/patologia , Humanos , Hidrogéis/química , Lactente , Masculino , Nanoestruturas/química , Veículos Farmacêuticos/química , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Pele/patologia , Neoplasias Cutâneas/patologia
11.
Biomater Sci ; 12(5): 1131-1150, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38284828

RESUMO

Extracellular vesicles (EVs) are vesicles with lipid bilayer structures shed from the plasma membrane of cells. Microvesicles (MVs) are a subset of EVs containing proteins, lipids, nucleic acids, and other metabolites. MVs can be produced under specific cell stimulation conditions and isolated by modern separation technology. Due to their tumor homing and large volume, tumor cell-derived microvesicles (TMVs) have attracted interest recently and become excellent delivery carriers for therapeutic vaccines, imaging agents or antitumor drugs. However, preparing sufficient and high-purity TMVs and conducting clinical transformation has become a challenge in this field. In this review, the recent research achievements in the generation, isolation, characterization, modification, and application of TMVs in cancer therapy are reviewed, and the challenges facing therapeutic applications are also highlighted.


Assuntos
Micropartículas Derivadas de Células , Vesículas Extracelulares , Neoplasias , Humanos , Micropartículas Derivadas de Células/química , Micropartículas Derivadas de Células/metabolismo , Micropartículas Derivadas de Células/patologia , Vesículas Extracelulares/química , Neoplasias/tratamento farmacológico , Membrana Celular
12.
Adv Healthc Mater ; : e2304087, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531346

RESUMO

Volumetric muscle loss (VML) is a severe form of muscle trauma that exceeds the regenerative capacity of skeletal muscle tissue, leading to substantial functional impairment. The abnormal immune response and excessive reactive oxygen species (ROS) accumulation hinder muscle regeneration following VML. Here, an interfacial cross-linked hydrogel-poly(ε-caprolactone) nanofiber composite, that incorporates both biophysical and biochemical cues to modulate the immune and ROS microenvironment for enhanced VML repair, is engineered. The interfacial cross-linking is achieved through a Michael addition between catechol and thiol groups. The resultant composite exhibits enhanced mechanical strength without sacrificing porosity. Moreover, it mitigates oxidative stress and promotes macrophage polarization toward a pro-regenerative phenotype, both in vitro and in a mouse VML model. 4 weeks post-implantation, mice implanted with the composite show improved grip strength and walking performance, along with increased muscle fiber diameter, enhanced angiogenesis, and more nerve innervation compared to control mice. Collectively, these results suggest that the interfacial cross-linked nanofiber-hydrogel composite could serve as a cell-free and drug-free strategy for augmenting muscle regeneration by modulating the oxidative stress and immune microenvironment at the VML site.

13.
J Colloid Interface Sci ; 672: 266-278, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38843679

RESUMO

Diabetic wound, which is chronic skin disease, poses a significant challenge in clinical practice because of persistent inflammation and impaired angiogenesis. Recently, hydrogen has emerged as a novel therapeutic agent due to its superior antioxidant and anti-inflammatory properties. In this study, we engineered a poly (lactic-co-glycolic acid) (PLGA) electrospun nanofibre membrane loaded with citric acid (CA) and iron (Fe) nanoparticles, referred to as Fe@PLGA + CA. Our in vitro assays demonstrated that the Fe@PLGA + CA membrane continuously generated and released hydrogen molecules via a chemical reaction between Fe and CA in an acidic microenvironment created by CA. We also discovered that hydrogen can ameliorate fibroblast migration disorders by reducing the levels of matrix metalloproteinase 9 (MMP9). Furthermore, we confirmed that hydrogen can scavenge or biochemically neutralise accumulated reactive oxygen species (ROS), inhibit pro-inflammatory responses, and induce anti-inflammatory reactions. This, in turn, promotes vessel formation, wound-healing and accelerates skin regeneration. These findings open new possibilities for using elemental iron in skin dressings and bring us one step closer to implementing hydrogen-releasing biomedical materials in clinical practice.

14.
J Control Release ; 367: 791-805, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38341179

RESUMO

Epidural fibrosis (EF), associated with various biological factors, is still a major troublesome clinical problem after laminectomy. In the present study, we initially demonstrate that sensory nerves can attenuate fibrogenic progression in EF animal models via the secretion of calcitonin gene-related peptide (CGRP), suggesting a new potential therapeutic target. Further studies showed that CGRP could inhibit the reprograming activation of fibroblasts through PI3K/AKT signal pathway. We subsequently identified metformin (MET), the most widely prescribed medication for obesity-associated type 2 diabetes, as a potent stimulator of sensory neurons to release more CGRP via activating CREB signal way. We copolymerized MET with innovative polycaprolactone (PCL) nanofibers to develop a metformin-grafted PCL nanoscaffold (METG-PCLN), which could ensure stable long-term drug release and serve as favorable physical barriers. In vivo results demonstrated that local implantation of METG-PCLN could penetrate into dorsal root ganglion cells (DRGs) to promote the CGRP synthesis, thus continuously inhibit the fibroblast activation and EF progress for 8 weeks after laminectomy, significantly better than conventional drug loading method. In conclusion, this study reveals the unprecedented potential of sensory neurons to counteract EF through CGRP signaling and introduces a novel strategy employing METG-PCLN to obstruct EF by fine-tuning sensory nerve-regulated fibrogenesis.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Diabetes Mellitus Tipo 2 , Poliésteres , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Fosfatidilinositol 3-Quinases , Fibrose , Fibroblastos/metabolismo
15.
J Colloid Interface Sci ; 648: 287-298, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37301153

RESUMO

Gene delivery for non-small-cell lung cancer treatment has been a challenge due to low nucleic acid binding ability, cell-wall barrier, and high cytotoxicity. Cationic polymers, such as the traditional "golden standard" polyethyleneimine (PEI) 25 kDa have emerged as a promising carrier for non-coding RNA delivery. However, the high cytotoxicity associated with its high molecular weight has limited its application in gene delivery. To address this limitation, herein, we designed a novel delivery system using fluorine-modified polyethyleneimine (PEI) 1.8 kDa for microRNA-942-5p-sponges non-coding RNA delivery. Compared to PEI 25 kDa, this novel gene delivery system demonstrated an approximately six-fold enhancement in endocytosis capability and maintain a higher cell viability. In vivo studies also showed good biosafety and anti-tumor effects, attribute to the positive charge of PEI and the hydrophobic and oleophobic properties of the fluorine-modified group. This study provides an effective gene delivery system for non-small-cell lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Transfecção , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Polietilenoimina/química , Flúor , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Técnicas de Transferência de Genes , MicroRNAs/genética , RNA não Traduzido
16.
Biomater Sci ; 11(15): 5301-5319, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37357799

RESUMO

Liver cancer (LC), one of the most common malignant primary tumors, presents a poor prognosis, high morbidity rate, and poor clinical outcomes. Despite conventional treatments have been applied prior to the deterioration, their clinical benefits were still limited. Arsenic trioxide (ATO), a toxic Chinese medicine, has been proven to efficiently inhibit the growth of LC both in vitro and in vivo. However, its therapeutic effects are hindered by poor pharmacokinetics and dose-limited toxicity. In this study, we developed a pH-responsive nanoplatform (PEG-MSN@ATO) consisting of mesoporous silica nanoparticles (MSN) that were modified with amino groups, loaded with ATO, and grafted with PEG to achieve the pH-triggered release and regulate CD8+ T cells and Treg cells in the tumor microenvironment (TME). PEG-MSN@ATO were characterized by uniform size, good loading efficiency, pH-responsive release features, decreased macrophage uptake, and enhanced dendritic cell activation in vitro. Furthermore, in vivo studies demonstrated that PEG-MSN@ATO enhanced the antitumor efficacy by inducing apoptosis and ROS production, inhibiting tumor cell proliferation and metastasis, and activating antitumor immunity within the TME. PEG-MSN@ATO also reduced the system toxicity of ATO by controlling the pH-trigger release in the tumor site. These results indicate that the PEG-MSN@ATO represents a promising drug delivery platform for reducing toxicity and enhancing the therapeutic efficacy of ATO against LC.


Assuntos
Neoplasias Hepáticas , Nanopartículas , Humanos , Trióxido de Arsênio/uso terapêutico , Dióxido de Silício , Linfócitos T CD8-Positivos , Portadores de Fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/tratamento farmacológico , Concentração de Íons de Hidrogênio , Microambiente Tumoral
17.
Biomater Adv ; 155: 213683, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925825

RESUMO

Liver cancer is among the leading cause of cancer related death worldwide. There is growing interest in using traditional Chinese medicines such as arsenic trioxide (ATO) to treat liver cancer. ATO have attracted attention due to its wide range of anti-cancer activities. However, the current ATO formulations are associated with drawbacks such as short half-life, lack of targeting ability towards solid tumors and apparent toxic side effects. Tumor microvesicles (TMVs) has shown encouraging results for the delivery of drugs to solid tumor. In this work, we designed ATO loaded TMVs further modified by SP94 peptide as liver cancer specific ligand (ATO@SP94-TMVs). This drug delivery system utilized SP94 peptide that selectively targets liver cancer cells while TMVs increase the accumulation of ATO at tumor site and activate immune response owing to the associated antigens. ATO@SP94-TMVs exhibited high encapsulation efficiency and tumor microenvironment triggered enhanced release of ATO in vitro. Cytotoxicity and uptake studies revealed remarkable inhibition and specific targeting of H22 cells. In addition, excellent immune response was detected in vitro, enhancing anti-tumor efficacy. Furthermore, a tumor inhibition rate of about 53.23 % was observed in H22 bearing tumor model. Overall, these results confirm that ATO@SP94-TMVs can be a promising nano drug delivery system for the future liver cancer therapy and improve its clinical applications.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias Hepáticas , Humanos , Trióxido de Arsênio/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Peptídeos/uso terapêutico , Microambiente Tumoral
18.
J Colloid Interface Sci ; 646: 399-412, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37207422

RESUMO

Graphdiyne (GDY) is a kind of nanomaterial from the graphene carbon family with excellent physical and chemical properties. Despite some applications in medical engineering, GDY has not been used as an electroactive scaffold for tissue regeneration because of its unclear in vitro and in vivo biosafety profiles. Here, a conductive GDY nanomaterial-loaded polycaprolactone (PCL) scaffold was prepared by electrospinning technique. For the first time, the biocompatibility of GDY-based scaffold was assessed at the cellular and animal levels in a peripheral nerve injury (PNI) model. The findings indicated that the conductive three-dimensional (3D) GDY/PCL nerve guide conduits (NGCs) could significantly improve the proliferation, adhesion and glial expression of Schwann cells (SCs). The conduits were implanted into a rat 10-mm sciatic nerve defect model for 3 months in vivo. The toxicity of scaffolds to the organs was negligible, while the GDY/PCL NGCs significantly promoted myelination and axonal growth by upregulating the expression levels of SC marker (S100 ß protein), Myelin basic protein (MBP), and axon regeneration marker (ß3-tubulin protein (Tuj1) and neurofilament protein 200 (NF200)). In addition, upregulation of vascular factor expression in GDY/PCL NGC group suggested the potential role in angiogenesis to improve nerve repair by GDY nanomaterials. Our findings provide new perspectives on biocompatibility and effectiveness of GDY nanomaterial scaffold in peripheral nerve regeneration for preclinical application.


Assuntos
Grafite , Nanofibras , Ratos , Animais , Grafite/farmacologia , Grafite/química , Ratos Sprague-Dawley , Alicerces Teciduais/química , Nanofibras/química , Axônios , Regeneração Nervosa/fisiologia
19.
J Mater Chem B ; 11(48): 11552-11561, 2023 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-37982207

RESUMO

Low efficiency of nerve growth and unstable release of loaded drugs have become a major problem in repairing peripheral nerve injury. Many intervention strategies were focused on simple drug loading, but have still been less effective. The key challenge is to establish a controlled release microenvironment to enable adequate nerve regeneration. In this study, we fabricate a multilayered compound nerve scaffold by electrospinning: with an anti-adhesive outer layer of polycaprolactone and an ECM-like inner layer consisting of a melatonin-loaded alginate hydrogel. We characterized the scaffold, and the loaded melatonin can be found to undergo controlled release. We applied them to a 15 mm rat model of sciatic nerve injury. After 16 weeks, the animals in each group were evaluated and compared for recovery of motor function, electrophysiology, target organ atrophy status, regenerative nerve morphology and relative protein expression levels of neural markers, inflammatory oxidative stress, and angiogenesis. We identify that the scaffold can improve functional ability evidenced by an increased sciatic functional index and nerve electrical conduction level. The antioxidant melatonin loaded in the scaffold reduces inflammation and oxidative stress in the reinnervated nerves, confirmed by increased HO-1 and decreased TNF-α levels in regenerating nerves. The relative expression of fast-type myosin was elevated in the target gastrocnemius muscle. An improvement in angiogenesis facilitates neurite extension and axonal sprouting. This scaffold can effectively restore the ECM-like microenvironment and improve the quality of nerve regeneration by controlled melatonin release, thus enlightening the design criteria on nerve scaffolds for peripheral nerve injury in the future.


Assuntos
Melatonina , Traumatismos dos Nervos Periféricos , Ratos , Animais , Melatonina/farmacologia , Hidrogéis/farmacologia , Nervo Isquiático/fisiologia , Preparações de Ação Retardada/farmacologia , Alicerces Teciduais , Regeneração Nervosa , Matriz Extracelular
20.
Eur J Pharm Biopharm ; 177: 273-288, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35868489

RESUMO

With the rapid increase in multidrug-resistance against antibiotics, higher doses of antibiotics or more effective antibiotics are needed to treat diseases, which ultimately leads to a decrease in the body's immunity and seriously threatens human health worldwide. The efficiency of antibiotics has been a large challenge for years. To overcome this problem, many carriers are utilized for anti-bacteria, attempting to optimize the delivery of such drugs and transport them safely and directly to the site of disease. Blood cell-based drug delivery systems present several advantages as compared to polymeric delivery system. These blood cells including red blood cells (RBCs), leukocytes, platelets. The blood cells and their membranes can both be used as drug carriers to deliver antibacterial drugs. In addition, blood cells can overcome many physiological/pathological obstacles faced by nanoparticles in vivo and effectively deliver drugs to the site of the disease. In this paper, we review studies on blood cell-based delivery systems used in antibacterial therapy, and analyze different roles in antibacterial therapy, which provide basis for further study in this field.


Assuntos
Biomimética , Nanopartículas , Antibacterianos/uso terapêutico , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Eritrócitos , Humanos
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