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1.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112176, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34785423

RESUMO

Although safe and eco-friendly botanical pesticides have been intensively promoted to combat pest attacks in agriculture, but their stability and efficacies remain an issue for their wide acceptability as sustained and effective approaches. The purpose of this work was to develop stable neem oil based nano-emulsion (NE) formulation with enhanced activity employing suitable bio-inspired adjuvant. So, Neem NEs (with and without) natural adjuvants (Cymbopogon citratus and Prosopis juliflora) in different concentrations were prepared and quality parameters dictating kinetic stability, acidity/alkalinity, viscosity, droplet size, zeta potential, surface tension, stability and compatibility were monitored using Viscometer, Zetasizer, Surface Tensiometer, High Performance Liquid Chromatography (HPLC) and Fourier Transform Infrared Spectroscopy (FTIR). Nano-emulsion biosynthesis optimization studies suggested that slightly acidic (5.9-6.5) NE is kinetically stable with no phase separation; creaming or crystallization may be due to botanical adjuvant (lemongrass oil). Findings proved that Prosopis juliflora, acted as bio-polymeric adjuvant to stabilize NE by increasing Brownian motion and weakening the attractive forces with smaller droplets (25-50 nm), low zeta potential (-30 mV) and poly-dispersive index (<0.3). Botanical adjuvant (30%) based NE with optimum viscosity (98.8cPs) can give long term storage stability and improved adhesiveness and wetting with reduced surface tension and contact angle. FT-IR analysis assured azadirachtin's stability and compatibility with adjuvant. With negligible degradation (1.42%) and higher half-life (t1/2) of 492.95 days, natural adjuvant based NE is substantially stable formulation, may be due to presence of glycosidic and phenolics compounds. Neem 20NE (with 30% adjuvant) exhibited remarkable insecticidal activity (91.24%) against whitefly (Bemisia tabaci G.) in brinjal (Solanum melongena) as evidenced by in-vivo assay. Results thus obtained suggest, bio-pesticide formulation may be used as safer alternative to chemical pesticides to minimize pesticide residues and presence of natural adjuvant may improves the stability and efficacy of biopesticides for safe crop protection in organic agriculture and Integrated Pest Management.


Assuntos
Adjuvantes Imunológicos , Controle de Insetos , Bioengenharia , Emulsões , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Microbiol Res ; 254: 126901, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34700186

RESUMO

In the light of intensification of cropping practices and changing climatic conditions, nourishing a growing global population requires optimizing environmental sustainability and reducing ecosystem impacts of food production. The use of microbiological systems to ameliorate the agricultural production in a sustainable and eco-friendly way is widespread accepted as a future key-technology. However, the multitude of interaction possibilities between the numerous beneficial microbes and plants in their habitat calls for systematic analysis and management of the rhizospheric microbiome. This review exploits present and future strategies for rhizospheric microbiome management with the aim to generate a comprehensive understanding of the known tools and techniques. Significant information on the structure and dynamics of rhizospheric microbiota of isolated microbial communities is now available. These microbial communities have beneficial effects including increased plant growth, essential nutrient acquisition, pathogens tolerance, and increased abiotic as well as biotic stress tolerance such as drought, temperature, salinity and antagonistic activities against the phyto-pathogens. A better and comprehensive understanding of the various effects and microbial interactions can be gained by application of molecular approaches as extraction of DNA/RNA and other biochemical markers to analyze microbial soil diversity. Novel techniques like interactome network analysis and split-ubiquitin system framework will enable to gain more insight into communication and interactions between the proteins from microbes and plants. The aim of the analysis tasks leads to the novel approach of Rhizosphere microbiome engineering. The capability of forming the rhizospheric microbiome in a defined way will allow combining several microbes (e.g. bacteria and fungi) for a given environment (soil type and climatic zone) in order to exert beneficial influences on specific plants. This integration will require a large-scale effort among academic researchers, industry researchers and farmers to understand and manage interactions of plant-microbiomes within modern farming systems, and is clearly a multi-domain approach and can be mastered only jointly by microbiology, mathematics and information technology. These innovations will open up a new avenue for designing and implementing intensive farming microbiome management approaches to maximize resource productivity and stress tolerance of agro-ecosystems, which in return will create value to the increasing worldwide population, for both food production and consumption.


Assuntos
Agricultura , Microbiota , Rizosfera , Desenvolvimento Sustentável , Agricultura/tendências , Bioengenharia/tendências , Produtos Agrícolas/microbiologia , Interações Microbianas , Microbiologia do Solo , Desenvolvimento Sustentável/tendências
5.
IEEE Pulse ; 12(5): 27-29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34784268

RESUMO

One of the core missions of the IEEE Engineering in Medicine and Biology Society (EMBS) is to be a platform for enhancing the personal and professional development of its members. This month we focus on two related priority areas of the IEEE EMBS Student Activities Committee (SAC) [1], namely Leadership Development and Professional Development Portfolios, and bring you up close to the student and professional leaders actively building these programs. The Leadership Development Portfolio, currently led by Agnieszka Lach from Silesian University of Technology, Gliwice, Poland, focuses on nurturing and supporting student leaders of the EMBS globally. The Professional Development Portfolio, currently led by Josée Rosset from the University of Manitoba, Winnipeg, MB, Canada, aims to help EMBS student members develop their skills and experiences in the practice of biomedical engineering.


Assuntos
Medicina , Estudantes de Medicina , Bioengenharia , Engenharia Biomédica , Engenharia , Humanos , Liderança
6.
7.
Biomater Sci ; 9(23): 8032-8050, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34723312

RESUMO

Control of cell-surface interaction is necessary for biomaterial applications such as cell sheets, intelligent cell culture surfaces, or functional coatings. In this paper, we propose the emergent property of cell morphology as a design parameter in the bioengineering of cell-biomaterial surface interactions. Cell morphology measured through various parameters can indicate ideal candidates for these various applications thus reducing the time taken for the screening and development process. The hypothesis of this study is that there is an optimal cell morphology range for enhanced cell proliferation and migration on the surface of biomaterials. To test the hypothesis, primary porcine dermal fibroblasts (PDF, 3 biological replicates) were cultured on ten different surfaces comprising components of the natural extracellular matrix of tissues. Results suggested an optimal morphology with a cell aspect ratio (CAR) between 0.2 and 0.4 for both increased cell proliferation and migration. If the CAR was below 0.2 (very elongated cell), cell proliferation was increased whilst migration was reduced. A CAR of 0.4+ (rounded cell) favoured cell migration over proliferation. The screening process, when it comes to biomaterials is a long, repetitive, arduous but necessary event. This study highlights the beneficial use of testing the cell morphology on prospective prototypes, eliminating those that do not support an optimal cell shape. We believe that the research presented in this paper is important as we can help address this screening inefficiency through the use of the emergent property of cell morphology. Future work involves automating CAR quantification for high throughput screening of prototypes.


Assuntos
Materiais Biocompatíveis , Bioengenharia , Animais , Movimento Celular , Forma Celular , Estudos Prospectivos , Suínos
8.
Int J Mol Sci ; 22(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34639050

RESUMO

Porous silicon is of current interest for cardiac tissue engineering applications. While porous silicon is considered to be a biocompatible material, it is important to assess whether post-etching surface treatments can further improve biocompatibility and perhaps modify cellular behavior in desirable ways. In this work, porous silicon was formed by electrochemically etching with hydrofluoric acid, and was then treated with oxygen plasma or supercritical carbon dioxide (scCO2). These processes yielded porous silicon with a thickness of around 4 µm. The different post-etch treatments gave surfaces that differed greatly in hydrophilicity: oxygen plasma-treated porous silicon had a highly hydrophilic surface, while scCO2 gave a more hydrophobic surface. The viabilities of H9c2 cardiomyocytes grown on etched surfaces with and without these two post-etch treatments was examined; viability was found to be highest on porous silicon treated with scCO2. Most significantly, the expression of some key genes in the angiogenesis pathway was strongly elevated in cells grown on the scCO2-treated porous silicon, compared to cells grown on the untreated or plasma-treated porous silicon. In addition, the expression of several apoptosis genes were suppressed, relative to the untreated or plasma-treated surfaces.


Assuntos
Materiais Biocompatíveis/química , Dióxido de Carbono/química , Miócitos Cardíacos , Silício/química , Bioengenharia , Sobrevivência Celular , Porosidade , Análise Espectral , Propriedades de Superfície
9.
Chem Soc Rev ; 50(22): 12551-12575, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34604889

RESUMO

Nucleic acids, with the advantages of programmability and biocompatibility, have been widely used to design different kinds of novel biocomputing devices. Recently, nucleic acid-based molecular computing has shown promise in making the leap from the test tube to the cell. Such molecular computing can perform logic analysis within the confines of the cellular milieu with programmable modulation of biological functions at the molecular level. In this review, we summarize the development of nucleic acid-based biocomputing devices that are rationally designed and chemically synthesized, highlighting the ability of nucleic acid-based molecular computing to achieve cellular applications in sensing, imaging, biomedicine, and bioengineering. Then we discuss the future challenges and opportunities for cellular and in vivo applications. We expect this review to inspire innovative work on constructing nucleic acid-based biocomputing to achieve the goal of precisely rewiring, even reconstructing cellular signal networks in a prescribed way.


Assuntos
Computadores Moleculares , Ácidos Nucleicos , Bioengenharia , DNA , Lógica
10.
J Vis Exp ; (175)2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34633382

RESUMO

Many developments in biomedical research have been inspired by discovering anatomical and cellular mechanisms that support specific functions in different species. The octopus is one of these exceptional animals that has given scientists new insights into the fields of neuroscience, robotics, regenerative medicine, and prosthetics. Research with this species of cephalopods requires the set-up of complex facilities and intensive care for both the octopus and its ecosystem that is critical for the project's success. This system requires multiple mechanical and biological filtering systems to provide a safe and clean environment for the animal. Along with the control system, specialized routine maintenance and cleaning are required to effectively keep the facility operating long term. It is advised to provide an enriched environment to these intelligent animals by changing the tank's landscape, incorporating a variety of prey, and introducing challenging tasks for them to work through. Our results include MRI and a whole-body autofluorescence imaging as well as behavioral studies to better understand their nervous system. Octopuses possess unique physiology that can impact many areas of biomedical research. Providing them with a sustainable ecosystem is the first crucial step in uncovering their distinct capabilities.


Assuntos
Octopodiformes , Robótica , Animais , Bioengenharia , Engenharia Biomédica , Ecossistema
11.
Micron ; 151: 103160, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34678583

RESUMO

Light influences most ecosystems on earth, from sun-dappled forests to bioluminescent creatures in the ocean deep. Biologists have long studied nano- and micro-scale organismal adaptations to manipulate light using ever-more sophisticated microscopy, spectroscopy, and other analytical equipment. In combination with experimental tools, simulations of light interacting with objects can help researchers determine the impact of observed structures and explore how variations affect optical function. In particular, the finite-difference time-domain (FDTD) method is widely used throughout the nanophotonics community to efficiently simulate light interacting with a variety of materials and optical devices. More recently, FDTD has been used to characterize optical adaptations in nature, such as camouflage in fish and other organisms, colors in sexually-selected birds and spiders, and photosynthetic efficiency in plants. FDTD is also common in bioengineering, as the design of biologically-inspired engineered structures can be guided and optimized through FDTD simulations. Parameter sweeps are a particularly useful application of FDTD, which allows researchers to explore a range of variables and modifications in natural and synthetic systems (e.g., to investigate the optical effects of changing the sizes, shape, or refractive indices of a structure). Here, we review the use of FDTD simulations in biology and present a brief methods primer tailored for life scientists, with a focus on the commercially available software Lumerical FDTD. We give special attention to whether FDTD is the right tool to use, how experimental techniques are used to acquire and import the structures of interest, and how their optical properties such as refractive index and absorption are obtained. This primer is intended to help researchers understand FDTD, implement the method to model optical effects, and learn about the benefits and limitations of this tool. Altogether, FDTD is well-suited to (i) characterize optical adaptations and (ii) provide mechanistic explanations; by doing so, it helps (iii) make conclusions about evolutionary theory and (iv) inspire new technologies based on natural structures.


Assuntos
Biomimética , Ecossistema , Animais , Bioengenharia , Simulação por Computador , Refratometria
12.
Adv Exp Med Biol ; 1345: 35-46, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582012

RESUMO

Since lung tissue is not able to be reconstructed after substantial injury, lung transplantation often is the only alternative for treatment. Antibiotic-resistant organisms that remain in donor lungs causing infection in the immunosuppressed recipient are among the complications following transplantation. Development of strategies for whole lung regeneration is a pleasing choice particularly in patients with end-stage lung diseases. Reconstruction of lung tissue in vitro for transplantation received increased attention which could deal with the shortage of donor organs. Recent advancements in the field of tissue engineering and regenerative medicine have paved the road for beneficial alternative therapies. Our group has extensive experience with regard to the structure of the lung tissue, which makes us to our decision to continue with the preparation of lung, with the aim of developing a new ECM scaffold. Herein, we aim to review the state-of-art and the tissue engineering and regenerative medicine technology highlighting the major achievements toward the production of a bioengineered lung obtained decellularization and recellularization techniques. We have strong hopes that recent developments in the engineering of lung will lead to similar breakthroughs in the engineering of distal lung components in the future.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Bioengenharia , Matriz Extracelular , Humanos , Pulmão
13.
Adv Exp Med Biol ; 1345: 47-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582013

RESUMO

The field of tissue engineering and regenerative medicine is able to depict the mechanism of cardiac repair and development of cardiac function as well, in order to reveal findings to new therapeutic designs for clinical treatment. The foremost approach of this scientific field is the fabrication of scaffolds, which contain cells that can be used as cardiac grafts in the body, to have the preferred recovery. Cardiac tissue engineering has not been completely organized for routine clinical usages. Hence, engineering innovations hold promise to character research and treatment options in the years to come. Our group has extensive experience with regard to the structure of the heart, which makes us to our decision to continue with the preparation of heart, with the aim of developing a new ECM scaffold. Herein, we aim to assess the state-of-the-art fabrication methods, advances in decellularization and recellularization techniques. We also highlight the major achievements toward the production of a bioengineered heart obtained from decellularization and recellularization techniques.


Assuntos
Transplante de Coração , Tecidos Suporte , Bioengenharia , Matriz Extracelular , Humanos , Doadores de Tecidos , Engenharia Tecidual
14.
Adv Exp Med Biol ; 1345: 61-70, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34582014

RESUMO

Natural scaffold appears to have extensive functions in providing anchorage and structural requirements, as well as providing a structural support for cell adherence and cell interaction for further recellularization process. Specific methods used for decellularization process play an essential role in the efficacy of cell removal and successful preservation of ultrastructure and biomechanical properties of the tissue. Numerous scaffolding materials and fabrication techniques have been investigated for pancreatic tissue engineering. Techniques of casting, freeze drying, injection molding, and electrospinning have been also used to fabricate scaffolds. Herein, we aim to review the state-of-the-art and the tissue engineering and regenerative medicine technology highlighting the major achievements toward the production of a bioengineered pancreas obtained decellularization techniques and cell-on-scaffold technology.


Assuntos
Matriz Extracelular , Tecidos Suporte , Bioengenharia , Pâncreas , Engenharia Tecidual
15.
Nat Commun ; 12(1): 5623, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561461

RESUMO

Patient-derived in vivo models of human cancer have become a reality, yet their turnaround time is inadequate for clinical applications. Therefore, tailored ex vivo models that faithfully recapitulate in vivo tumour biology are urgently needed. These may especially benefit the management of pancreatic ductal adenocarcinoma (PDAC), where therapy failure has been ascribed to its high cancer stem cell (CSC) content and high density of stromal cells and extracellular matrix (ECM). To date, these features are only partially reproduced ex vivo using organoid and sphere cultures. We have now developed a more comprehensive and highly tuneable ex vivo model of PDAC based on the 3D co-assembly of peptide amphiphiles (PAs) with custom ECM components (PA-ECM). These cultures maintain patient-specific transcriptional profiles and exhibit CSC functionality, including strong in vivo tumourigenicity. User-defined modification of the system enables control over niche-dependent phenotypes such as epithelial-to-mesenchymal transition and matrix deposition. Indeed, proteomic analysis of these cultures reveals improved matrisome recapitulation compared to organoids. Most importantly, patient-specific in vivo drug responses are better reproduced in self-assembled cultures than in other models. These findings support the use of tuneable self-assembling platforms in cancer research and pave the way for future precision medicine approaches.


Assuntos
Bioengenharia/métodos , Carcinoma Ductal Pancreático/patologia , Modelos Biológicos , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Células Estromais/patologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Técnicas de Cultura de Células/métodos , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Reprodutibilidade dos Testes , Células Estromais/metabolismo , Células Tumorais Cultivadas
16.
Nat Commun ; 12(1): 5603, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556652

RESUMO

Although the first dissection of the human ovary dates back to the 17th century, the biophysical characteristics of the ovarian cell microenvironment are still poorly understood. However, this information is vital to deciphering cellular processes such as proliferation, morphology and differentiation, as well as pathologies like tumor progression, as demonstrated in other biological tissues. Here, we provide the first readout of human ovarian fiber morphology, interstitial and perifollicular fiber orientation, pore geometry, topography and surface roughness, and elastic and viscoelastic properties. By determining differences between healthy prepubertal, reproductive-age, and menopausal ovarian tissue, we unravel and elucidate a unique biophysical phenotype of reproductive-age tissue, bridging biophysics and female fertility. While these data enable to design of more biomimetic scaffolds for the tissue-engineered ovary, our analysis pipeline is applicable for the characterization of other organs in physiological or pathological states to reveal their biophysical markers or design their bioinspired analogs.


Assuntos
Ovário/anatomia & histologia , Ovário/fisiologia , Adulto , Fatores Etários , Idoso , Bioengenharia , Criança , Pré-Escolar , Tecido Elástico/anatomia & histologia , Tecido Elástico/metabolismo , Elasticidade , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Feminino , Hormônios/metabolismo , Humanos , Pessoa de Meia-Idade , Folículo Ovariano/crescimento & desenvolvimento , Reserva Ovariana , Ovário/citologia , Viscosidade , Adulto Jovem
17.
Cells ; 10(9)2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34572137

RESUMO

Inherited retinal degenerations (IRD) affecting either photoreceptors or pigment epithelial cells cause progressive visual loss and severe disability, up to complete blindness. Retinal organoids (ROs) technologies opened up the development of human inducible pluripotent stem cells (hiPSC) for disease modeling and replacement therapies. However, hiPSC-derived ROs applications to IRD presently display limited maturation and functionality, with most photoreceptors lacking well-developed outer segments (OS) and light responsiveness comparable to their adult retinal counterparts. In this review, we address for the first time the microenvironment where OS mature, i.e., the subretinal space (SRS), and discuss SRS role in photoreceptors metabolic reprogramming required for OS generation. We also address bioengineering issues to improve culture systems proficiency to promote OS maturation in hiPSC-derived ROs. This issue is crucial, as satisfying the demanding metabolic needs of photoreceptors may unleash hiPSC-derived ROs full potential for disease modeling, drug development, and replacement therapies.


Assuntos
Bioengenharia/métodos , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Organoides/citologia , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/citologia , Animais , Humanos , Degeneração Retiniana/patologia
18.
PLoS One ; 16(9): e0256805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34473741

RESUMO

Fishways have been widely used for upstream passage around human-built structures, but 'success' has varied dramatically. Evaluation of fishway success has typically been conducted at local scales using metrics such as fish passage efficiency and passage time, but evaluations are increasingly used in broader assessments of whether passage facilities meet population-specific conservation and management objectives. Over 15 years, we monitored passage effectiveness at eight dams on the Columbia and Snake rivers for 26,886 radio-tagged spring-summer and fall Chinook Salmon O. tshwaytscha, Sockeye Salmon O. nerka, and summer steelhead O. mykiss during their migrations to spawning sites. Almost all fish that entered dam tailraces eventually approached and entered fishways. Tailrace-to-forebay passage efficiency estimates at individual dams were consistently high, averaging 0.966 (SD = 0.035) across 245 run×year×dam combinations. These estimates are among the highest recorded for any migratory species, which we attribute to the scale of evaluation, salmonid life history traits (e.g., philopatry), and a sustained adaptive management approach to fishway design, maintenance, and improvement. Full-dam fish passage times were considerably more variable, with run×year×dam medians ranging from 5-65 h. Evaluation at larger scales provided evidence that fishways were biologically effective, e.g., we observed rapid migration rates (medians = 28-40 km/d) through river reaches with multiple dams and estimated fisheries-adjusted upstream migration survival of 67-69%. However, there were substantive uncertainties regarding effectiveness. Uncertainty about natal origins confounded estimation of population-specific survival and interpretation of apparent dam passage 'failure', while lack of post-migration reproductive data precluded analyses of delayed or cumulative effects of passing the impounded system on fish fitness. Although the technical fishways are effective for salmonids in the Columbia-Snake River system, other co-migrating species have lower passage rates, highlighting the need for species-specific design and evaluation wherever passage facilities impact fish management and conservation goals.


Assuntos
Migração Animal/fisiologia , Conservação dos Recursos Naturais/métodos , Espécies em Perigo de Extinção , Pesqueiros , Oncorhynchus mykiss/fisiologia , Rios , Salmão/fisiologia , Animais , Bioengenharia/métodos , Feminino , Humanos , Masculino , Estações do Ano , Especificidade da Espécie , Telemetria/métodos
19.
Immunity ; 54(8): 1636-1651, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34348117

RESUMO

The development of effective vaccines to combat infectious diseases is a complex multi-year and multi-stakeholder process. To accelerate the development of vaccines for coronavirus disease 2019 (COVID-19), a novel pathogen emerging in late 2019 and spreading globally by early 2020, the United States government (USG) mounted an operation bridging public and private sector expertise and infrastructure. The success of the endeavor can be seen in the rapid advanced development of multiple vaccine candidates, with several demonstrating efficacy and now being administered around the globe. Here, we review the milestones enabling the USG-led effort, the methods utilized, and ensuing outcomes. We discuss the current status of COVID-19 vaccine development and provide a perspective for how partnership and preparedness can be better utilized in response to future public-health pandemic emergencies.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pesquisa , SARS-CoV-2/imunologia , Bioengenharia , Biotecnologia , Vacinas contra COVID-19/administração & dosagem , Humanos , Modelos Moleculares , Avaliação de Resultados em Cuidados de Saúde , Vigilância em Saúde Pública , Pesquisa/estatística & dados numéricos , Pesquisa/tendências , Estados Unidos/epidemiologia , Cobertura Vacinal/estatística & dados numéricos , Vacinologia
20.
Theranostics ; 11(16): 8043-8056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335979

RESUMO

Rationale: As a potentially life-threatening disorder, cerebral ischemia-reperfusion (I/R) injury is associated with significantly high mortality, especially the irreversible brain tissue damage associated with increased reactive oxygen radical production and excessive inflammation. Currently, the insufficiency of targeted drug delivery and "on-demand" drug release remain the greatest challenges for cerebral I/R injury therapy. Bioengineered cell membrane-based nanotherapeutics mimic and enhance natural membrane functions and represent a potentially promising approach, relying on selective interactions between receptors and chemokines and increase nanomedicine delivery efficiency into the target tissues. Methods: We employed a systematic method to synthesize biomimetic smart nanoparticles. The CXCR4-overexpressing primary mouse thoracic aorta endothelial cell (PMTAEC) membranes and RAPA@HOP were extruded through a 200 nm polycarbonate porous membrane using a mini-extruder to harvest the RAPA@BMHOP. The bioengineered CXCR4-overexpressing cell membrane-functionalized ROS-responsive nanotherapeutics, loaded with rapamycin (RAPA), were fabricated to enhance the targeted delivery to lesions with pathological overexpression of SDF-1. Results: RAPA@BMHOP exhibited a three-fold higher rate of target delivery efficacy via the CXCR4/SDF-1 axis than its non-targeting counterpart in an in vivo model. Additionally, in response to the excessive pathological ROS, nanotherapeutics could be degraded to promote "on-demand" cargo release and balance the ROS level by p-hydroxy-benzyl alcohol degradation, thereby scavenging excessive ROS and suppressing the free radical-induced focal damage and local inflammation. Also, the stealth effect of cell membrane coating functionalization on the surface resulted in extended circulation time and high stability of nanoparticles. Conclusion: The biomimetic smart nanotherapeutics with active targeting, developed in this study, significantly improved the therapeutic efficacy and biosafety profiles. Thus, these nanoparticles could be a candidate for efficient therapy of cerebral I/R injury.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Receptores CXCR4/metabolismo , Traumatismo por Reperfusão/terapia , Animais , Bioengenharia/métodos , Materiais Biomiméticos/farmacologia , Isquemia Encefálica/metabolismo , Membrana Celular/metabolismo , Liberação Controlada de Fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanomedicina/métodos , Nanopartículas/administração & dosagem , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Receptores CXCR4/genética , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia
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