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1.
Mol Pharm ; 21(6): 3006-3016, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698500

RESUMO

Unlocking the potential of metal nanoparticles (NPs) in biomedical applications represents a leading endeavor in contemporary research. Among these, gold NPs (AuNPs) and silver NPs (AgNPs) have shown promising strides in combatting complex neurodegenerative ailments like Alzheimer's disease. Yet, the unexplored realm of bimetallic Au/Ag-NP harbors immense potential, concealing undiscovered opportunities for enhanced therapeutic effectiveness through the synergistic interaction of metal ions. Nonetheless, the limitations of traditional synthesis methods have restricted the preparation, biocompatibility, and versatility of these NPs, prompting an urgent requirement for innovative approaches. Biobased synthetic methodologies have emerged as a noteworthy solution to address these challenges. Our study ventures into uncharted terrain, harnessing collagen-mimicking peptide nanofibers as a bioactive template for the synthesis of bimetallic NPs. These green NPs exhibit remarkable activity in inhibiting amyloid ß (Aß) protein aggregation with almost 74% inhibition, surpassing the individual impacts of Au and Ag NPs, which show inhibition percentages of 66 and 43, respectively. The bimetallic Au/Ag-NPs not only demonstrate powerful inhibition of Aß, but they also demonstrate inhibitory activity against esterase (∼50%) and against reactive oxygen species (ROS) (∼75%), metamorphosing into multifaceted therapeutic agents for Alzheimer's disease. Au/Ag-NPs have proven highly beneficial in surpassing cellular barriers, as evidenced by studies on tissue penetration, 3D uptake, and endosomal escape, and these attributes also hold promise for the future treatment modalities. The findings indicate that the intrinsic traits of Au/Ag-NPs provide numerous mechanistic benefits, such as inhibiting Aß and acetylcholinesterase (AChE), and reducing stress related to ROS, in addition to their advantageous internalization properties. This research represents a notable advancement in the development of multitargeted treatments for neurodegenerative disorders using bimetallic NPs, diverging from the prevalent emphasis on AuNPs in the current literature.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Ouro , Nanopartículas Metálicas , Prata , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Nanopartículas Metálicas/química , Ouro/química , Prata/química , Peptídeos beta-Amiloides/metabolismo , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo
2.
Macromol Biosci ; 23(7): e2300057, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37097091

RESUMO

The major drawbacks of metal-based implants are weak osseointegration and post-operational infections. These limitations restrict the long-term use of implants that may cause severe tissue damage and replacement of the implant. Recent strategies to enhance the osseointegration process require an elaborate fabrication process and suffer from post-operative complications. To address the current challenges taking inspiration from the extracellular matrix (ECM), the current study is designed to establish enhanced osseointegration with lowered risk of infection. Natural biopolymer pectin, peptide amphiphiles, and enzyme-mimicking fullerene moieties are governed to present an ECM-like environment around the implant surfaces. This multifunctional approach promotes osseointegration via inducing biomineralization and osteoblast differentiation. Application of the biopolymer-based composite to the metal surfaces significantly enhances cellular attachment, supports the mineral deposition, and upregulates osteoblast-specific gene expression. In addition to the osteoinductive properties of the constructed layers, the inherent antimicrobial properties of multilayer coating are also used to prevent infection possibility. The reported biopolymer-artificial enzyme composite demonstrates antimicrobial activity against Escherichia coli and Bacillus subtilis as a multifunctional surface coating.


Assuntos
Anti-Infecciosos , Implantes Dentários , Osseointegração , Peptídeos/farmacologia , Anti-Infecciosos/farmacologia , Biopolímeros/farmacologia , Titânio/farmacologia , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
3.
Int J Biol Macromol ; 233: 123604, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36773861

RESUMO

As has been reported many times before, the two-dimensional (2D) cell culture techniques used today are far from modeling native tissue environments. Therefore, tremendous amounts of effort were devoted to developing three-dimensional (3D) cell cultures with high tissue resemblance. Whereas, these techniques suffer from elaborate preparation processes, batch-to-batch variations, unnatural components, chemical modifications, side products, static culture conditions, or complex reactor systems. To overcome these limitations, we report an undocumented one-step strategy to create a tissue-like 3D cell culture method by mimicking the extracellular matrix (ECM) microenvironment with rapid, non-covalent cross-linking of biopolymer-peptide complex and recently designed non-static cell culturing modules. In the current method, we prepared a very facile and tailorable ECM-like network by using easily attainable building blocks without the need for chemical modifications and possible undesirable/noncontrollable responses resulting from these unnatural modifications. Cells encapsulated in this new biopolymer mesh were located in the swimming culture module to mimic not only the microenvironment but also the non-static physical environment of the ECM. The feasibility of this method was analyzed on a bio-regeneration model; SaOS-2 cells cultured in the current 3D system induced improved osteogenic regeneration. The ECM resemblance of the method was also exhibited by histological sections of the cells incubated in the recent gel formulation. Furthermore, different cell types derived from various tissues could be cultured in our recent ECM model, which could be very practicable for personalized test models for future applications as a replacement for animal studies.


Assuntos
Hidrogéis , Nanofibras , Animais , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Pectinas/metabolismo , Matriz Extracelular/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo
4.
Macromol Biosci ; 22(9): e2200079, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35751428

RESUMO

Enzyme mimicry is a topic of considerable interest in the development of multifunctional biomimetic materials. Mimicking enzyme activity is a major challenge in biomaterials research, and artificial analogs that simultaneously recapitulate the catalytic and metabolic activity of native enzymes are considered to be the ultimate goal of this field. This consensus may be challenged by self-assembling multifunctional nanostructures to develop close-to-fidelity enzyme mimics. Here, the ability of fullerene nanostructures decorated with active units to form enzyme-like materials that can mimic phosphatases in a metal-free manner is presented. These nanostructures self-assemble into nanoclusters forming multiple random active sites that can cleave both phosphomonoesters and phosphodiesters while being more specific for the phosphomonoesters. Moreover, they are reusable and show an increase in catalytic activity over multiple cycles similar to their natural counterparts. In addition to having enzyme-like catalytic properties, these nanocatalysts imitate the biological functions of their natural analogs by inducing biomineralization and osteoinduction in preosteoblast and mesenchymal stem cells in vitro studies.


Assuntos
Materiais Biomiméticos , Fulerenos , Células-Tronco Mesenquimais , Nanoestruturas , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Fulerenos/farmacologia , Nanoestruturas/química , Osteogênese
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