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1.
Drug Resist Updat ; 75: 101098, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38833804

RESUMO

Breakthroughs in actual clinical applications have begun through vaccine-based cancer immunotherapy, which uses the body's immune system, both humoral and cellular, to attack malignant cells and fight diseases. However, conventional vaccine approaches still face multiple challenges eliciting effective antigen-specific immune responses, resulting in immunotherapy resistance. In recent years, biomimetic nanovaccines have emerged as a promising alternative to conventional vaccine approaches by incorporating the natural structure of various biological entities, such as cells, viruses, and bacteria. Biomimetic nanovaccines offer the benefit of targeted antigen-presenting cell (APC) delivery, improved antigen/adjuvant loading, and biocompatibility, thereby improving the sensitivity of immunotherapy. This review presents a comprehensive overview of several kinds of biomimetic nanovaccines in anticancer immune response, including cell membrane-coated nanovaccines, self-assembling protein-based nanovaccines, extracellular vesicle-based nanovaccines, natural ligand-modified nanovaccines, artificial antigen-presenting cells-based nanovaccines and liposome-based nanovaccines. We also discuss the perspectives and challenges associated with the clinical translation of emerging biomimetic nanovaccine platforms for sensitizing cancer cells to immunotherapy.


Assuntos
Células Apresentadoras de Antígenos , Vacinas Anticâncer , Imunoterapia , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia/métodos , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Nanopartículas/administração & dosagem , Células Apresentadoras de Antígenos/imunologia , Biomimética/métodos , Materiais Biomiméticos/administração & dosagem , Animais , Lipossomos , Nanovacinas
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124559, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38830331

RESUMO

In this work, we present a novel colorimetric sensing platform for the sensitive detection of ethamsylate (ETM) usingultrathin MnO2 nanosheets with enhancedoxidase-mimicking activity. A facile template-free hydrothermal process was applied to synthesize the MnO2 nanosheets under mild conditions. The nanosheets exhibited oxidase-mimicking activity, facilitating the conversion of TMB into the blue-colored oxTMB in the absence of H2O2. However, the presence of ETM inhibited this activity, resulting in the conversion of oxTMB back to colorless TMB and a substantial decrease in the blue color intensity. The colorimetric response exhibited a linear relationship with ETM concentration over the range of 0.5 to 10.0 µg/mL and a detection limit of 0.156 µg/mL. To further elucidate the underlying mechanism, we performed extensive characterization and kinetic experiments. The findings demonstrated that this unique property is attributed to the remarkable capacity of the MnO2 nanosheets to absorb oxygen, producing superoxide radicals (O2-). The oxidase-mimicking activity of the nanosheets was further confirmed by the reaction kinetics, following Michaelis-Menten's behavior. Moreover, the applicability of the sensing platform was assessed by determining ETM concentrations in various real samples (different pharmaceuticals, human plasma, and environmental water). The well-established platform demonstrates the prospective role that nanomaterials-based sensing platforms may play in clinical diagnostics, pharmaceutical analysis, and other relevant fields.


Assuntos
Colorimetria , Limite de Detecção , Compostos de Manganês , Nanoestruturas , Óxidos , Oxirredutases , Colorimetria/métodos , Compostos de Manganês/química , Óxidos/química , Nanoestruturas/química , Oxirredutases/metabolismo , Oxirredutases/química , Cinética , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Materiais Biomiméticos/química , Benzidinas/química
3.
Int J Mol Sci ; 25(11)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38891788

RESUMO

In the process of tissue engineering, several types of stresses can influence the outcome of tissue regeneration. This outcome can be understood by designing hydrogels that mimic this process and studying how such hydrogel scaffolds and cells behave under a set of stresses. Here, a hydrogel formulation is proposed to create biomimetic scaffolds suitable for fibroblast cell culture. Subsequently, we examine the impact of external stresses on fibroblast cells cultured on both solid and porous hydrogels. These stresses included mechanical tension and altered-gravity conditions experienced during the 83rd parabolic flight campaign conducted by the European Space Agency. This study shows distinct cellular responses characterized by cell aggregation and redistribution in regions of intensified stress concentration. This paper presents a new biomimetic hydrogel that fulfills tissue-engineering requirements in terms of biocompatibility and mechanical stability. Moreover, it contributes to our comprehension of cellular biomechanics under diverse gravitational conditions, shedding light on the dynamic cellular adaptations versus varying stress environments.


Assuntos
Fibroblastos , Hidrogéis , Engenharia Tecidual , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/citologia , Hidrogéis/química , Engenharia Tecidual/métodos , Técnicas de Cultura de Células/métodos , Estresse Mecânico , Biomimética/métodos , Animais , Alicerces Teciduais/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Humanos , Camundongos
4.
Drug Deliv ; 31(1): 2354687, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38823413

RESUMO

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Diterpenos , Compostos de Epóxi , Neoplasias Hepáticas , Nanopartículas , Fenantrenos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Diterpenos/administração & dosagem , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/farmacocinética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Compostos de Epóxi/química , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/farmacologia , Fenantrenos/administração & dosagem , Fenantrenos/farmacologia , Fenantrenos/química , Fenantrenos/farmacocinética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Camundongos , Membrana Celular/efeitos dos fármacos , Tamanho da Partícula , Portadores de Fármacos/química , Camundongos Nus , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos Endogâmicos BALB C
5.
Carbohydr Polym ; 339: 122232, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823905

RESUMO

In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.


Assuntos
Alginatos , Regeneração Óssea , Quitosana , Hidrogéis , Álcool de Polivinil , Engenharia Tecidual , Alicerces Teciduais , Quitosana/química , Alginatos/química , Alginatos/farmacologia , Álcool de Polivinil/química , Alicerces Teciduais/química , Humanos , Regeneração Óssea/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Engenharia Tecidual/métodos , Nanotubos de Carbono/química , Osteoblastos/efeitos dos fármacos , Osteoblastos/citologia , Grafite/química , Grafite/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular
6.
Mol Pharm ; 21(7): 3577-3590, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38857525

RESUMO

Triple-negative breast cancer (TNBC) is characterized by high malignancy and limited treatment options. Given the pressing need for more effective treatments for TNBC, this study aimed to develop platelet membrane (PM)-camouflaged silver metal-organic framework nanoparticles (PM@MOF-Ag NPs), a biomimetic nanodrug. PM@MOF-Ag NP construction involved the utilization of 2-methylimidazole and silver nitrate to prepare silver metal-organic framework (MOF-Ag) NPs. The PM@MOF-Ag NPs, due to their camouflage, possess excellent blood compatibility, immune escape ability, and a strong affinity for 4T1 tumor cells. This enhances their circulation time in vivo and promotes the aggregation of PM@MOF-Ag NPs at the 4T1 tumor site. Importantly, PM@MOF-Ag NPs demonstrated promising antitumor activity in vitro and in vivo. We further revealed that PM@MOF-Ag NPs induced tumor cell death by overproducing reactive oxygen species and promoting cell apoptosis. Moreover, PM@MOF-Ag NPs enhanced apoptosis by upregulating the ratios of Bax/Bcl-2 and cleaved caspase3/pro-caspase3. Notably, PM@MOF-Ag NPs exhibited no significant organ toxicity, whereas the administration of MOF-Ag NPs resulted in liver inflammation compared to the control group.


Assuntos
Apoptose , Nanopartículas Metálicas , Estruturas Metalorgânicas , Espécies Reativas de Oxigênio , Prata , Neoplasias de Mama Triplo Negativas , Estruturas Metalorgânicas/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Animais , Feminino , Prata/química , Camundongos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Biomimética/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Nanopartículas/química
7.
ACS Appl Mater Interfaces ; 16(25): 32599-32610, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38862125

RESUMO

Hydrogels are soft materials engineered to suit a multitude of applications that exploit their tunable mechanochemical properties. Dynamic hydrogels employing noncovalent, physically cross-linked networks dominated by either enthalpic or entropic interactions enable unique rheological and stimuli-responsive characteristics. In contrast to enthalpy-driven interactions that soften with increasing temperature, entropic interactions result in largely temperature-independent mechanical properties. By engineering interfacial polymer-particle interactions, we can induce a dynamic-to-covalent transition in entropic hydrogels that leads to biomimetic non-ergodic aging in the microstructure without altering the network mesh size. This transition is tuned by varying temperature and formulation conditions such as pH, which allows for multivalent tunability in properties. These hydrogels can thus be designed to exhibit either temperature-independent metastable dynamic cross-linking or time-dependent stiffening based on formulation and storage conditions, all while maintaining structural features critical for controlling mass transport, akin to many biological tissues. Such robust materials with versatile and adaptable properties can be utilized in applications such as wildfire suppression, surgical adhesives, and depot-forming injectable drug delivery systems.


Assuntos
Hidrogéis , Hidrogéis/química , Materiais Biomiméticos/química , Concentração de Íons de Hidrogênio , Temperatura , Reologia , Biomimética/métodos
8.
Nanoscale ; 16(25): 11863-11878, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38841898

RESUMO

Red blood cells (RBCs), which function as material transporters in organisms, are rich in materials that are exchanged with metabolically active tumor cells. Recent studies have demonstrated that tumor cells can regulate biological changes in RBCs, including influencing differentiation, maturation, and morphology. RBCs play an important role in tumor development and immune regulation. Notably, the novel scientific finding that RBCs absorb fragments of tumor-carrying DNA overturns the conventional wisdom that RBCs do not contain nucleic acids. RBC membranes are excellent biomimetic materials with significant advantages in terms of their biocompatibility, non-immunogenicity, non-specific adsorption resistance, and biodegradability. Therefore, RBCs provide a new research perspective for the development of tumor liquid biopsies, molecular imaging, drug delivery, and other tumor precision diagnosis and treatment technologies.


Assuntos
Eritrócitos , Neoplasias , Humanos , Eritrócitos/metabolismo , Neoplasias/terapia , Neoplasias/diagnóstico , Neoplasias/patologia , Medicina de Precisão , Animais , Sistemas de Liberação de Medicamentos , Membrana Eritrocítica/química , Membrana Eritrocítica/metabolismo , Materiais Biomiméticos/química
9.
Biosens Bioelectron ; 261: 116501, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38905858

RESUMO

A novel laccase mimic enzyme Cu-Mn with excellent photothermal properties was firstly prepared via a combination of hydrothermal and in situ synthesis. Cu-Mn nanozymes could catalyze the typical laccase substrate 2,4-dichlorophenol (2,4-DP) to generate the red quinone imine. Further, loading the MnO2 nanosheets with photothermal properties, Cu-Mn nanozymes possessed not only excellent laccase catalytic activity, but also high photothermal conversion efficiency. The presence of glutathione S-transferase (GST) recovered the glutathione (GSH)-induced weakness of the laccase activity and photothermal properties of Cu-Mn. Hence, a GST enzyme-regulated dual-mode sensing strategy was established based on Cu-Mn nanozymes. The detection limits of GST monitoring based on colorimetric and photothermal methods were 0.092 and 0.087 U/L with response times of 20 min and 8 min, respectively. Furthermore, the proposed method enabled the measuring of GST levels in human serum and was successfully employed in the primary evaluation of hepatitis patients. Another attraction, the impressive photothermal behavior also endowed the Cu-Mn nanozymes with promising antimicrobial properties, which exhibited significant antimicrobial effects against Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus). Unsurprisingly, multifunctional Cu-Mn nanozymes certainly explore new paths in biochemical analysis and antimicrobial applications.


Assuntos
Antibacterianos , Técnicas Biossensoriais , Cobre , Escherichia coli , Glutationa Transferase , Lacase , Staphylococcus aureus , Lacase/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Glutationa Transferase/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Catálise , Oxirredução , Limite de Detecção , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Clorofenóis/farmacologia , Clorofenóis/química , Colorimetria/métodos , Óxidos/química , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Nanoestruturas/química
10.
Biosens Bioelectron ; 261: 116491, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879900

RESUMO

As one class of molecular imprinted polymers (MIPs), surface imprinted polymer (SIP)-based biosensors show great potential in direct whole-bacteria detection. Micro-contact imprinting, that involves stamping the template bacteria immobilized on a substrate into a pre-polymerized polymer matrix, is the most straightforward and prominent method to obtain SIP-based biosensors. However, the major drawbacks of the method arise from the requirement for fresh template bacteria and often non-reproducible bacteria distribution on the stamp substrate. Herein, we developed a positive master stamp containing photolithographic mimics of the template bacteria (E. coli) enabling reproducible fabrication of biomimetic SIP-based biosensors without the need for the "real" bacteria cells. By using atomic force and scanning electron microscopy imaging techniques, respectively, the E. coli-capturing ability of the SIP samples was tested, and compared with non-imprinted polymer (NIP)-based samples and control SIP samples, in which the cavity geometry does not match with E. coli cells. It was revealed that the presence of the biomimetic E. coli imprints with a specifically designed geometry increases the sensor E. coli-capturing ability by an "imprinting factor" of about 3. These findings show the importance of geometry-guided physical recognition in bacterial detection using SIP-based biosensors. In addition, this imprinting strategy was employed to interdigitated electrodes and QCM (quartz crystal microbalance) chips. E. coli detection performance of the sensors was demonstrated with electrochemical impedance spectroscopy (EIS) and QCM measurements with dissipation monitoring technique (QCM-D).


Assuntos
Aderência Bacteriana , Técnicas Biossensoriais , Escherichia coli , Polímeros , Escherichia coli/isolamento & purificação , Polímeros/química , Impressão Molecular/métodos , Propriedades de Superfície , Polímeros Molecularmente Impressos/química , Infecções por Escherichia coli/microbiologia , Materiais Biomiméticos/química
11.
Bioinspir Biomim ; 19(4)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38870926

RESUMO

In order to enhance energy absorption, this study draws inspiration from the diagonal bilinear robust square lattice structure found in deep-sea glass sponges, proposing a design for thin-walled structures with superior folding capabilities and high strength-to-weight ratio. Firstly, the crashworthiness of bionic glass sponge tube (BGSTO) is compared with that of equal-wall-thickness equal-mass four-X tube through both experiments and simulations, and it is obtained that the specific energy absorption of BGSTO is increased by 78.64%. And the crashworthiness of BGSTO is also most significant compared to that of multicellular tubes with the similar number of crystalline cells. Additionally, we found that the double-line spacing of the glass sponge can be freely adjusted without changing the material amount. Therefore, based on BGSTO, we designed two other double-line structures, BGSTA and BGSTB. Then with equal wall thickness and mass as a prerequisite, this study proceeds to design and compare the energy absorption properties of three bilinear thin-walled tubes in both axial and lateral cases. The deformation modes and crashworthiness of the three types of tubes with variable bilinear spacing (ßO/A/B) are comparatively analysed. The improved complex proportional assessment (COPRAS) synthesis decision is used to obtain that BGSTO exhibits superior crashworthiness over the remaining two kinds of tubes. Finally, a surrogate model is established to perform multi-objective optimization on the optimal bilinear configuration BGSTO selected by the COPRAS method.


Assuntos
Biônica , Poríferos , Poríferos/química , Animais , Materiais Biomiméticos/química , Simulação por Computador , Vidro/química , Biomimética/métodos
12.
Anal Chem ; 96(25): 10365-10372, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38869249

RESUMO

Biomimetic cytochrome P450 for chemical activation of environmental carcinogens is an efficient in vitro model for evaluating their mutagenicity and ultimately acquiring the metabolites that cannot be easily accessed by conventional routes of organic synthesis. Different kinds of mutagen derived from polyaromatic hydrocarbons (PAHs) by metalloporphyrin/oxidant model systems have been reported, but the underlying molecular mechanisms are poorly understood. Herein, we have for the first time demonstrated an effective surface-enhanced Raman scattering (SERS) protocol to study the dynamics and biomimetic metabolic behaviors of pyrene (Pyr) in the presence of various oxygen donors. Quantitative information on the relative concentration of Pyr and its metabolites in the biomimetic system can be extracted from the SERS spectra. On the basis of our results, we conclude that the oxidative metabolism of Pyr is highly influenced by the types and concentrations of oxygen donors, leading to the formation of 1-hydroxypyrene and dioxygenated products. Besides, the addition of an appropriate amount of an organic solvent can promote the formation of secondary oxidation products. These results offer valuable insights into the dynamics of PAHs metabolism and the regulation of their metabolic pathways in biomimetic activation. In comparison to traditional liquid chromatography-mass spectrometry, the present SERS approach is more suitable for high-throughput evaluation of the metabolic process and kinetics of PAHs. We anticipate that this approach will enable a more general and comprehensive tracking of metabolic dynamics and molecular mechanisms involved in the biomimetic activation of other xenobiotics, such as procarcinogens, promutagens, and drugs.


Assuntos
Pirenos , Análise Espectral Raman , Análise Espectral Raman/métodos , Cinética , Pirenos/química , Pirenos/metabolismo , Biomimética , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/metabolismo , Propriedades de Superfície , Ativação Metabólica , Sistema Enzimático do Citocromo P-450/metabolismo , Oxirredução
13.
Int J Nanomedicine ; 19: 5157-5172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855731

RESUMO

Background: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions-a phenomenon described as the "stealth effect". In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored. Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA). Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site. Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted.


Assuntos
Materiais Revestidos Biocompatíveis , Poliésteres , Polímeros , Soroalbumina Bovina , Stents , Poliésteres/química , Animais , Soroalbumina Bovina/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Polímeros/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Indóis/química , Indóis/farmacologia , Propriedades de Superfície , Humanos , Teste de Materiais , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos
14.
J Nanobiotechnology ; 22(1): 362, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38910259

RESUMO

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.


Assuntos
Lesão Pulmonar Aguda , Vesículas Extracelulares , Macrófagos , Camundongos Endogâmicos C57BL , MicroRNAs , Nanopartículas , Sepse , Animais , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Sepse/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , MicroRNAs/metabolismo , Camundongos , Nanopartículas/química , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Humanos , Masculino , Lipopolissacarídeos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Multiômica
15.
Int J Nanomedicine ; 19: 6177-6199, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911498

RESUMO

Purpose: Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration. Methods: MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated. Results: Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life. Conclusion: MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke.


Assuntos
Administração Intranasal , Barreira Hematoencefálica , Ginsenosídeos , AVC Isquêmico , Lipossomos , Macrófagos , Animais , Lipossomos/química , AVC Isquêmico/tratamento farmacológico , Ratos , Masculino , Ginsenosídeos/farmacocinética , Ginsenosídeos/química , Ginsenosídeos/administração & dosagem , Ginsenosídeos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Ratos Sprague-Dawley , Distribuição Tecidual , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Materiais Biomiméticos/administração & dosagem , Saponinas/farmacocinética , Saponinas/química , Saponinas/administração & dosagem , Saponinas/farmacologia , Camundongos
16.
ACS Appl Mater Interfaces ; 16(25): 32027-32044, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38867426

RESUMO

Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. ß-Cyclodextrin (ß-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. ß-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.


Assuntos
Aterosclerose , Materiais Biomiméticos , Colesterol , Dopamina , Macrófagos , Metotrexato , Nanopartículas , Dopamina/química , Dopamina/farmacologia , Nanopartículas/química , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Camundongos , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Metotrexato/química , Metotrexato/farmacologia , Colesterol/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Humanos , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Células RAW 264.7 , Estresse Oxidativo/efeitos dos fármacos , Portadores de Fármacos/química , beta-Ciclodextrinas
17.
J Am Chem Soc ; 146(25): 17201-17210, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38874405

RESUMO

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.


Assuntos
Antioxidantes , Dissecção Aórtica , Cobalto , Catálise , Cobalto/química , Cobalto/farmacologia , Dissecção Aórtica/tratamento farmacológico , Dissecção Aórtica/patologia , Antioxidantes/química , Antioxidantes/farmacologia , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/síntese química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas Metálicas/química
18.
Colloids Surf B Biointerfaces ; 240: 113979, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38823339

RESUMO

Atherosclerosis, the primary mechanism underlying the development of many cardiovascular illnesses, continues to be one of the leading causes of mortality worldwide. Platelet (PLT), which are essential for maintaining body homeostasis, have been strongly linked to the onset of atherosclerosis at various stages due to their inherent tendency to bind to atherosclerotic lesions and show an affinity for plaques. Therefore, mimicking PLT's innate adhesive features may be necessary to effectively target plaques. PLT-derived nanocarriers have emerged as a promising biomimetic targeting strategy for treating atherosclerosis due to their numerous advantages. These advantages include excellent biocompatibility, minimal macrophage phagocytosis, prolonged circulation time, targeting capability for impaired vascular sites, and suitability as carriers for anti-atherosclerotic drugs. Herein, we discuss the role of PLT in atherogenesis and propose the design of nanocarriers based on PLT-membrane coating and PLT-derived vesicles. These nanocarriers can target multiple biological elements relevant to plaque development. The review also emphasizes the current challenges and future research directions for the effective utilization of PLT-derived nanocarriers in treating atherosclerosis.


Assuntos
Aterosclerose , Biomimética , Plaquetas , Portadores de Fármacos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Humanos , Plaquetas/metabolismo , Plaquetas/efeitos dos fármacos , Portadores de Fármacos/química , Biomimética/métodos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Animais , Nanopartículas/química , Sistemas de Liberação de Medicamentos
19.
Lab Chip ; 24(13): 3276-3283, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38847088

RESUMO

Lipid nanoparticles often contain a phosphatidylcholine with a long chain fatty acid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). However, their preparation often encounters difficulties such as the inability to yield <20 nm nanoparticles due to the aggregation-prone behavior of DSPC. High-density lipoproteins (HDLs) are ∼10 nm protein-bound lipid nanoparticles in our body, and microfluidic preparations of HDL-mimicking nanoparticles (µHDL) have been reported. Herein, we report a new microfluidic mixing mode that enables preparation of µHDL with DSPC in high yield (≥90% on a protein basis). The critical mechanism of this mode is a spontaneous asymmetric distribution of the ethanol flow injected in a symmetric manner followed by turbulent mixing in a simple rectangular parallelepiped-shaped chip.


Assuntos
Lipoproteínas HDL , Técnicas Analíticas Microfluídicas , Nanopartículas , Fosfatidilcolinas , Fosfatidilcolinas/química , Nanopartículas/química , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Técnicas Analíticas Microfluídicas/instrumentação , Dispositivos Lab-On-A-Chip , Materiais Biomiméticos/química
20.
Int J Nanomedicine ; 19: 5523-5544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882544

RESUMO

Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.


Assuntos
Materiais Biomiméticos , Sistemas de Liberação de Medicamentos , Imidazóis , Estruturas Metalorgânicas , Nanopartículas , Zeolitas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacocinética , Humanos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacocinética , Zeolitas/química , Zeolitas/farmacocinética , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Imidazóis/química , Imidazóis/farmacocinética , Imidazóis/administração & dosagem , Animais , Zinco/química , Zinco/farmacocinética , Zinco/administração & dosagem , Biomimética/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Concentração de Íons de Hidrogênio
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