RESUMO
Adhesion to many kinds of surfaces, including biological tissues, is important in many fields but has been proved to be extremely challenging. Furthermore, peeling from strong adhesion is needed in many conditions, but is sometimes painful. Herein, a mussel inspired hydrogel is developed to achieve both strong adhesion and trigger-detachment. The former is actualized by electrostatic interactions, covalent bonds, and physical interpenetration, while the latter is triggered, on-demand, through combining a thixotropic supramolecular network and polymer double network. The results of the experiments show that the hydrogel can adhere to various material surfaces and tissues. Moreover, triggered by shear force, non-covalent interactions of the supramolecular network are destroyed. This adhesion can be peeled easily. The possible mechanism involved is discussed and proved. This work will bring new insight into electronic engineering and tissue repair like skin care for premature infants and burn victims.
Assuntos
Hidrogéis , Adesivos Teciduais , Adesivos , Humanos , Hidrogéis/química , Polímeros , Adesivos Teciduais/química , CicatrizaçãoRESUMO
Deep-level sensors for detecting the local temperatures of inner organs and tissues of an animal are rarely reported. In this paper, we present a method to fabricate multifunctional micro-probes with standard cleanroom procedures, using a piece of stainless-steel foil as the substrate. On each of the as-fabricated micro-probes, arrays of thermocouples made of Pd-Cr thin-film stripes with reliable thermal sensing functions were built, together with Pd electrode openings for detecting electrical signals. The as-fabricated sword-shaped freestanding microprobes with length up to 30 mm showed excellent mechanical strength and elastic properties when they were inserted into the brain and muscle tissues of live rats, as well as suitable electrochemical properties and, therefore, are promising for potential biological applications.
Assuntos
Técnicas Biossensoriais/métodos , Temperatura Corporal/fisiologia , Encéfalo/fisiologia , Músculos/fisiologia , Animais , Técnicas Eletroquímicas , Eletrodos , Humanos , Fenômenos Mecânicos , Nanopartículas Metálicas/química , Ratos , Aço Inoxidável/químicaRESUMO
Advanced drug delivery systems (DDS) enhance treatment efficacy of different therapeutics in a dosage, spatial, and/or temporal controlled manner. To date, numerous chemical- or physical-based stimuli-responsive formulations or devices for controlled drug release have been developed. Among them, the emerging mechanical force-based stimulus offers a convenient and robust controlled drug release platform and has attracted increasing attention. The relevant DDS can be activated to promote drug release by different types of mechanical stimuli, including compressive force, tensile force, and shear force as well as indirect formats, remotely triggered by ultrasound and magnetic field. In this review, we provide an overview of recent advances in mechanically activated DDS. The opportunities and challenges regarding clinical translations are also discussed.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Fenômenos Mecânicos , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Lipossomos/química , Lipossomos/farmacologia , Fenômenos Magnéticos , Microbolhas , Nanopartículas/química , Ondas UltrassônicasRESUMO
A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.
Assuntos
Portadores de Fármacos/química , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Animais , Glicemia/metabolismo , Hipóxia Celular , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Liberação Controlada de Fármacos , Glucose Oxidase/metabolismo , Células HeLa , Humanos , Hipoglicemiantes/química , Insulina/química , Masculino , Camundongos Endogâmicos C57BL , Nitroimidazóis/química , Oxirredução , Peptídeos/química , Polietilenoglicóis/químicaRESUMO
Polymersomes, the structural analogues of liposomes, are hollow structures enclosed by a bilayer membrane made from amphiphilic copolymers. Polymersomes have been proposed to mimic the structure and properties of cellular membranes and viral capsids. Excellent robustness and stability, chemical versatility for tunable membrane properties and surface functionalization make polymersomes attractive candidates for drug delivery, diagnostic imaging, nanoreactor vessels, and artificial organelles. In further biomimetic strategies, stimuli-responsive polymersomes that can recognize various external physical or internal biological environmental stimuli and conduct "on demand" release in dose-, spatial-, and temporal-controlled fashions have been widely developed. This Perspective focuses on recent advances in stimuli-responsive polymersomes and their potential biomedical applications. Representative examples of each stimulus, the advantages and limitations of different strategies, and the future opportunities and challenges are discussed.
Assuntos
Materiais Biomiméticos/química , Membranas Artificiais , Polímeros/química , Diagnóstico por Imagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
A photonic crystal (PC) sensor that can selectively detect organic vapors through visual color changes has been proposed. The sensor was fabricated by infiltrating a tetraphenylethene polymer (TPEP) into the voids of SiO2 inverse opal photonic crystal. When the sensor was exposed to tetrahydrofuran or acetone vapor, a red shift of the stopband of more than 50 nm could be clearly observed; meanwhile, the film's color changed from violet to cyan. Subsequently, when exposed to air, the stopband underwent a blue shift and the color returned to violet. The reason for the observed change is that a reversible adsorption-desorption process occurs on alternate exposure of the sensor to organic vapor and air, due to the high specific surface area of the inverse opal macroporous structure and the high affinity of TPEP to tetrahydrofuran and acetone. The adsorption of vapor analyte can increase the PC's effective refractive index, which will induce the stopband red shift and the resulting color change according to Bragg's Law. The reversible adsorption-desorption of organic vapors varied the effective refractive index of the sensor repeatedly, causing the reversible stopband shift and color change, and providing a general method for the design of visual vapor sensors.
Assuntos
Óptica e Fotônica/instrumentação , Polímeros/química , Dióxido de Silício/química , Compostos Orgânicos Voláteis/análise , Microscopia de Força Atômica , Modelos Moleculares , Sondas Moleculares/químicaRESUMO
This research proposes a simple and novel strategy for the green detection of antibiotics along with the reduction of microplastic and humic acid (HA) hazards. The entire process is based on a single-step solvent-sieving method to separate HA into insoluble (IHA) and soluble (SHA) components, subsequently recombining and designing the application according to the original characteristics of selected fractions in accordance with the zero-waste principle. IHA was applied as a dispersive solid phase extraction (DSPE) sorbent without chemical modification for the enrichment of trace MACs in complex biological matrices. The recovery of MACs was 74.06-100.84 % in the range of 2.5-1000 µgâkg-1. Furthermore, SHA could be combined with biodegradable polyvinyl alcohol (PVA) to prepare multifunctional composite films. SHA endows the PVA film with favorable mechanical properties, excellent UV shielding as well as oxidation resistance performance. Compared with pure PVA, the tensile strength, toughness, antioxidant and UV-protection properties were increased to 157.3 Mpa, 258.6 MJ·m-3, 78.6 % and 60 % respectively. This study achieved a green and economically valuable utilization of all components of waste HA, introduced a novel approach for monitoring and controlling harmful substances and reducing white pollution. This has significant implications for promoting sustainable development and recovering valuable resources.
Assuntos
Antibacterianos , Substâncias Húmicas , Álcool de Polivinil , Substâncias Húmicas/análise , Antibacterianos/química , Antibacterianos/análise , Álcool de Polivinil/química , Extração em Fase Sólida/métodos , Química Verde , Resistência à TraçãoRESUMO
Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or instead utilize existing extracellular matrix microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3-dimensional migration, few recapitulate these natural migration paths. Here, we develop a biopolymer-based bicontinuous hydrogel system that comprises a covalent hydrogel of enzymatically crosslinked gelatin and a physical hydrogel of guest and host moieties bonded to hyaluronic acid. Bicontinuous hydrogels form through controlled solution immiscibility, and their continuous subdomains and high micro-interfacial surface area enable rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior is mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which is shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a design that leverages important local interfaces to guide rapid cell migration.
Assuntos
Matriz Extracelular , Hidrogéis , Hidrogéis/química , Movimento Celular , Matriz Extracelular/metabolismo , Esferoides Celulares , Biopolímeros/metabolismoRESUMO
The pickling sludge produced in the stainless steel pickling process is a hazardous waste and disposal in landfill poses a potential environmental risk. Stainless steel pickling sludge contains metal elements such as Fe, Cr, and Ni and substances such as SiO2 and CaO, which have good value for resource recycling. This paper briefly introduces the generation, nature, and hazards of stainless steel pickling sludge; and clustering analysis of relevant literature keywords in recent years; and detailed analysis and comparison of sludge obtained from different steel mills and resource utilization process. The current situation of pickling sludge resource utilization and the development of relevant policies in China in recent years are summarized, and new thoughts on the direction of its resource utilization are put forward.
Assuntos
Esgotos , Aço Inoxidável , Dióxido de Silício , Aço , ChinaRESUMO
We have reported a hexaphenylsilole/polymethyl methacrylate (HPS/PMMA) composite film with a lotus-leaf-like structure shows highly stability and excellent sensitivities for metal ions (Fe3+ and Hg2+) a few years ago. In the above paper, it was considered that the special surface morphology is the important aspects which enhance the stability of the sensor. But it is still a lack of research on the sensing mechanism. In this paper, the sensing mechanism of fiber membrane is continuing to study in detail. The experimental results show that the electron-transfer mechanism is a crucial factor for the fluorescent quenching.
Assuntos
Membranas Artificiais , Metais/análise , Metais/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Espectrometria de Fluorescência/métodos , Cristalização/métodos , Íons , Teste de Materiais , Tamanho da PartículaRESUMO
Biosafety of AZ31B magnesium (Mg) alloy and the effect of its degradation products on tissues, organs, and whole systems are highly needed to be evaluated before clinical application. This study serves a wide variety of safety evaluations of biodegradable AZ31B alloy on nerve cells. As a result of this in vitro study, the maximum aluminum (Al) ion and Mg ion concentrations in the medium were estimated to be 22 µmol/L and 2.75 mmol/L, respectively, during degradation. In addition, the corresponding cell mortality was observed to be 36% and lower than 5% according to the resistance curves of the cell to Mg and Al ions. Furthermore, the maximum Al ion and Mg ion concentrations in serum and cerebrospinal fluid were detected to be 26.1 µmol/L and 1.2 mmol/L, respectively, for 5 months implantation. Combining the result of in vivo dialysis with the result of ion tolerance assay experiments, the actual death rate of nerve cells is estimated between 4 and 10% in vivo, which is lower than the result of in vitro cytotoxicity evaluation. Moreover, no psychomotor disability during clinical studies is observed. Consequently, stent made of AZ31B alloy with surface treatment is feasible for carotid artery stenosis, and it is safe in terms of cell viability on the nervous system.
Assuntos
Contenção de Riscos Biológicos , Magnésio , Ligas/farmacologia , Artérias Carótidas , Magnésio/farmacologia , Teste de Materiais , StentsRESUMO
BACKGROUND: The most common reconstruction method for bone defects caused by giant cell tumor of bone (GCTB) is cement packing combined with subchondral bone grafting and extra fixation. However, this method has several limitations involving bone cement and bone graft, which may lead to poor prognosis and joint function. A titanium-based 3D-printed strut-type prosthesis, featured with excellent biocompatibility and osseointegration ability, was developed for this bone defect in our institution. The goal of this study is to comparatively analyze the biomechanical performance of reconstruction methods aimed at the identification of better operative strategy. METHODS: Four different 3D finite element models were created. Model #1: Normal femur; Model #2: Femur with tumorous cavity bone defects in the distal femur; Model #3: Cavity bone defects reconstructed by cement packing combined with subchondral bone grafting and extra fixation; Model #4: Cavity bone defects reconstructed by 3D-printed strut-type prosthesis combined with subchondral bone grafting. The femoral muscle multiple forces were applied to analyze the mechanical difference among these models by finite element analysis. RESULTS: Optimal stress and displacement distribution were observed in the normal femur. Both reconstruction methods could provide good initial stability and mechanical support. Stress distributed unevenly on the femur repaired by cement packing combined with subchondral bone grafting and extra fixation, and obvious stress concentration was found around the articular surface of this femur. However, the femur repaired by 3D-printed strut-type prosthetic reconstruction showed better performance both in displacement and stress distribution, particularly in terms of the protection of articular surface and subchondral bone. CONCLUSIONS: 3D-printed strut-type prosthesis is outstanding in precise shape matching and better osseointegration. Compared to cement packing and extra fixation, it can provide the almost same support and fixation stiffness, but better biomechanical performance and protection of subchondral bone and articular cartilage. Therefore, 3D-printed strut-type prosthetic reconstruction combined with subchondral bone grafting may be evaluated as an alternative for the treatment of GCTBs in distal femur.
Assuntos
Cimentos Ósseos/uso terapêutico , Neoplasias Ósseas , Transplante Ósseo , Fêmur/cirurgia , Tumor de Células Gigantes do Osso , Adulto , Fenômenos Biomecânicos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Feminino , Fêmur/patologia , Tumor de Células Gigantes do Osso/patologia , Tumor de Células Gigantes do Osso/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Impressão Tridimensional , Próteses e Implantes , Desenho de PróteseRESUMO
The current preparation methods of carbon quantum dots (CDs) involve many reaction parameters, which leads to many possibilities in the synthesis processes and high uncertainty of the resultant production performance. Recently, machine learning (ML) methods have shown great potential in correlating the selected features in many applications, which can help understand the relevant structure-function relationships of CDs and discover better synthesis recipes as well. In this work, we employ the ML approach to guide the blue CD synthesis in microwave systems. After optimizing the synthesis parameters and conditions, the quantum yield (QY) increases to about 200% higher than the average value of the prepared samples without ML guidance. The obtained CDs are applied as fluorescent probes to monitor hydrogen peroxide (H2O2) in human teeth. The CD probe exhibits a linear relationship with the concentration of H2O2 ranging from 0 to 1.1 M with a lower detection limit of 0.12 M, which can effectively detect the residual H2O2 after bleaching teeth. This work shows that the adopted ML methods have considerable advantages in guiding the synthesis of high-quality CDs, which could accelerate the development of other novel functional materials in energy, biomedical, and environmental remediation applications.
Assuntos
Pontos Quânticos , Carbono , Corantes Fluorescentes , Humanos , Peróxido de Hidrogênio , Aprendizado de Máquina , Micro-OndasRESUMO
Insulin and glucagon secreted from the pancreas with dynamic balance play a vital role in regulating blood glucose levels. Although distinct glucose-responsive insulin delivery systems have been developed, the lack of a self-regulated glucagon release module limits their clinical applications due to the potential risk of hypoglycemia. Here, we describe a transdermal polymeric microneedle patch for glucose-responsive closed-loop insulin and glucagon delivery to achieve glycemic regulation with minimized risk of hypoglycemia. The glucose-responsive phenylboronic acid units can bind to glucose to reversibly shift the net charge (from positive to negative) of the entire polymeric matrix within microneedles. Therefore, the release ratio of the negatively charged insulin and the positively charged glucagon analog from the patch can be dynamically tuned upon the fluctuation of blood glucose levels to realize glycemic homeostasis. In both chemically induced type 1 diabetic mouse and minipig models, this glucose-responsive dual-hormone microneedle patch demonstrated tight long-term regulation in blood glucose levels (>24 hours in minipigs).
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Suínos , Animais , Camundongos , Glucagon , Glucose , Glicemia , Insulina , Porco Miniatura , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina , PolímerosRESUMO
Glucose-responsive insulin delivery systems that mimic insulin secretion activity in the pancreas show great potential to improve clinical therapeutic outcomes for people with type 1 and advanced type 2 diabetes. Here, we report a glucose-responsive insulin delivery microneedle (MN) array patch that is loaded with red blood cell (RBC) vesicles or liposome nanoparticles containing glucose transporters (GLUTs) bound with glucosamine-modified insulin (Glu-Insulin). In hyperglycemic conditions, high concentrations of glucose in interstitial fluid can replace Glu-Insulin via a competitive interaction with GLUT, leading to a quick release of Glu-Insulin and subsequent regulation of blood glucose (BG) levels in vivo. To prolong the effective glucose-responsive insulin release from MNs, additional free Glu-Insulin, which serves as "stored insulin", is loaded after RBC vesicles or liposome nanoparticles bound with Glu-Insulin. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, this smart GLUT-based insulin patch can effectively control BG levels without causing hypoglycemia.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Insulina/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/uso terapêutico , Lipossomos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glucose/metabolismo , Glicemia/metabolismo , AgulhasRESUMO
Microplastics (MPs) contain high levels of polybrominated diphenyl ethers (PBDEs), which can leach to organism tissues upon ingestion, thereby leading to increased chemical exposure. However, leaching kinetics of inherent contaminants from ingested MPs are poorly studied. The present study characterized the leaching kinetics of PBDEs from sub-millimeter sized MPs in fish oil at relevant body temperatures for marine organisms and assessed exposure risk of MPs for cod fish by a biodynamic model. Diffusion coefficients (Dp) of PBDEs are in the ranges of 1.98 × 10-19-2.35 × 10-16 m2·s-1 in polystyrene, 1.89 × 10-20-2.07 × 10-18 m2·s-1 in acrylonitrile butadiene styrene, and 4.26 × 10-18-1.72 × 10-15 m2·s-1 in polypropylene. A linear function obtained between log Dp of BDE-209 and glass-transition temperature of MPs allows estimation of Dp of BDE-209 contained in other common types of MPs present in the gastrointestinal lipid. The biota-plastic accumulation factors of PBDEs for three plastics were in the range of 4.77 × 10-14-4.03 × 10-7. Although bioaccumulation of MPs-affiliated PBDEs is accelerated by oil in the gastrointestinal tract, the modeled steady-state concentrations of PBDEs in cod tissue lipid through ingestion of MPs under the most likely conditions were below the lower end of the global PBDE concentration, implicating that ingestion of MPs by organisms remains a negligible pathway in general.
Assuntos
Éteres Difenil Halogenados , Poluentes Químicos da Água , Bioacumulação , Monitoramento Ambiental , Óleos de Peixe , Éteres Difenil Halogenados/análise , Cinética , Microplásticos , Plásticos , Poluentes Químicos da Água/análiseRESUMO
Developing biotemplating techniques to translate microorganisms and cultured mammalian cells into metallic biocomposites is of great interest for biosensors, electronics, and energy. The metallization of viruses and microbial cells is successfully demonstrated via a genetic engineering strategy or electroless deposition. However, it is difficult to transform mammalian cells into metallic biocomposites because of the complicated genes and the delicate morphological features. Herein, "polymer-assisted cell metallization" (PACM) is reported as a general method for the transformation of mammalian cells into metallic biocomposites. PACM includes a first step of in situ polymerization of functional polymer on the surface and in the interior of the mammalian cells, and a subsequent electroless deposition of metal to convert the polymer-functionalized cells into metallic biocomposites, which retain the micro- and nanostructures of the mammalian cells. This new biotemplating method is compatible with different cell types and metals to yield a wide variety of metallic biocomposites with controlled structures and properties.
Assuntos
Materiais Biocompatíveis/química , Metais/química , Polímeros/química , Animais , Sítios de Ligação , Cobre/química , Eletroquímica , Eletrônica , Ouro/química , Células HeLa , Humanos , Camundongos , Microscopia Confocal , Nanoestruturas/química , Níquel/química , Cifozoários , Prata/química , Propriedades de SuperfícieRESUMO
Accurate diagnosis and efficient treatment of tumors are highly significant in battling cancer. Near-infrared II (NIR-II) fluorescence imaging shows big promise for deep tumor visualization in living systems due to high temporal and spatial resolution and deep tissue penetration capability, whereas the development of efficient NIR-II probes for tumor theranostics still faces a huge challenge. Herein, we have designed and constructed intelligent mPEG5000-PCL3000-encapsulated NIR-II nanoprobe ZM1068-NPs that showed great chemical stability and excellent biocompatibility. With the merits of the strong fluorescence in the NIR-II region and prominent optical-thermal conversion efficiency, this probe was successfully used for NIR-II imaging-guided surgery and photothermal therapy of breast carcinoma in living mice. More notably, it was for the first time found that ZM1068 dyes could be covalently on-site-immobilized within tumors through the thiol-chlor nucleophilic substitution reaction, resulting in improved tumor accumulation and retention time. We thus envision that this probe may provide an attractive means for precise cancer diagnosis and treatment.
Assuntos
Corantes Fluorescentes/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/cirurgia , Polietilenoglicóis/química , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/uso terapêutico , Raios Infravermelhos , Camundongos , Nanopartículas/uso terapêutico , Imagem Óptica , Terapia Fototérmica , Polietilenoglicóis/uso terapêutico , Cirurgia Assistida por Computador , Nanomedicina TeranósticaRESUMO
Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs in vivo. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of â¼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (â¼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors in vivo. More excitingly, the Mn2+-chelating probe (Ce6-Leu@Mn2+) was demonstrated to have the capability to catalyze endogenous H2O2 to persistently release O2 at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment.
Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Glutationa/metabolismo , Leucil Aminopeptidase/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Nanomedicina Teranóstica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorofilídeos/química , Clorofilídeos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Teste de Materiais , Estrutura Molecular , Imagem Óptica , Tamanho da Partícula , Fármacos Fotossensibilizantes/químicaRESUMO
Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.