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1.
Prog Polym Sci ; 1332022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37779922

RESUMO

Recent advances in materials science and engineering highlight the importance of designing sophisticated biomaterials with well-defined architectures and tunable properties for emerging biomedical applications. Click chemistry, a powerful method allowing specific and controllable bioorthogonal reactions, has revolutionized our ability to make complex molecular structures with a high level of specificity, selectivity, and yield under mild conditions. These features combined with minimal byproduct formation have enabled the design of a wide range of macromolecular architectures from quick and versatile click reactions. Furthermore, copper-free click chemistry has resulted in a change of paradigm, allowing researchers to perform highly selective chemical reactions in biological environments to further understand the structure and function of cells. In living systems, introducing clickable groups into biomolecules such as polysaccharides (PSA) has been explored as a general approach to conduct medicinal chemistry and potentially help solve healthcare needs. De novo biosynthetic pathways for chemical synthesis have also been exploited and optimized to perform PSA-based bioconjugation inside living cells without interfering with their native processes or functions. This strategy obviates the need for laborious and costly chemical reactions which normally require extensive and time-consuming purification steps. Using these approaches, various PSA-based macromolecules have been manufactured as building blocks for the design of novel biomaterials. Clickable PSA provides a powerful and versatile toolbox for biomaterials scientists and will increasingly play a crucial role in the biomedical field. Specifically, bioclick reactions with PSA have been leveraged for the design of advanced drug delivery systems and minimally invasive injectable hydrogels. In this review article, we have outlined the key aspects and breadth of PSA-derived bioclick reactions as a powerful and versatile toolbox to design advanced polymeric biomaterials for biomedical applications such as molecular imaging, drug delivery, and tissue engineering. Additionally, we have also discussed the past achievements, present developments, and recent trends of clickable PSA-based biomaterials such as 3D printing, as well as their challenges, clinical translatability, and future perspectives.

2.
Cell Mol Neurobiol ; 42(4): 1125-1139, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33222099

RESUMO

The current study aimed to determine the protective effect of AY9944 related to Caveolin-1 and Claudin-5 role in lipid raft, which can rescue the blood-brain barrier from enhanced permeability. Therefore, in vivo analyses were performed following ischemia in normal, ischemic, and AY9944-treated animal groups. The results revealed that AY9944 reduced the infarct size, edema, and brain water content. The extravasation of Alb-Alexa 594 and biocytin-TMR was minimum in the AY9944-treated animals. The results showed a significant decrease in the expression level of Caveolin-1 over 8 h and 48 h and a remarkable increase in the level of Claudin-5 over 48 h following ischemia in AY9944-treated animals. Molecular docking simulation demonstrated that AY9944 exerts a possible protective role via attenuating the interaction of the Caveolin-1 and cholesterol in lipid raft. These findings point out that AY9944 plays a protective role in stroke by means of blood-brain barrier preservation. Proper neural function essentially needs a constant homeostatic brain environment which is provided by the blood-brain barrier. Rescuing blood-brain barrier from enhanced permeability via inducing the protective effect of AY9944 related to caveolin-1 and claudin-5 role in lipid raft was the aim of the current study.


Assuntos
Barreira Hematoencefálica , Caveolina 1 , Animais , Caveolina 1/metabolismo , Claudina-5/metabolismo , Simulação de Acoplamento Molecular , Permeabilidade , Dicloridrato de trans-1,4-Bis(2-clorobenzaminometil)ciclo-hexano/metabolismo , Dicloridrato de trans-1,4-Bis(2-clorobenzaminometil)ciclo-hexano/farmacologia
3.
Crit Rev Food Sci Nutr ; 62(13): 3658-3697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33399020

RESUMO

The therapeutic effects of carotenoids as dietary supplements to control or even treat some specific diseases including diabetic retinopathy, cardiovascular diseases, bacterial infections, as well as breast, prostate, and skin cancer are discussed in this review and also thoughts on future research for their widespread use are emphasized. From the stability standpoint, carotenoids have low bioavailability and bioaccessibility owing to their poor water solubility, deterioration in the presence of environmental stresses such as oxygen, light, and high heat as well as rapid degradation during digestion. Nanoencapsulation technologies as wall or encapsulation materials have been increasingly used for improving food product functionality. Nanoencapsulation is a versatile process employed for the protection, entrapment, and the delivery of food bioactive products including carotenoids from diverse environmental conditions for extended shelf lives and for providing controlled release. Therefore, we present here, recent (mostly during the last five years) nanoencapsulation methods of carotenoids with various nanocarriers. To us, this review can be considered as the first highlighting not only the potential therapeutic effects of carotenoids on various diseases but also their most effective nanodelivery systems.HighlightsBioactive compounds are of deep interest to improve food properties.Carotenoids (such as ß-carotene and xanthophylls) play indispensable roles in maintaining human health and well-being.A substantial research effort has been carried out on developing beneficial nanodelivery systems for various carotenoids.Nanoencapsulation of carotenoids can enhance their functional properties.Stable nanoencapsulated carotenoids could be utilized in food products.


Assuntos
Carotenoides , Sistemas de Liberação de Fármacos por Nanopartículas , Disponibilidade Biológica , Suplementos Nutricionais , Excipientes , Humanos
4.
J Chem Technol Biotechnol ; 97(7): 1640-1654, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35463806

RESUMO

The application of quantum dots (QDs) for detecting and treating various types of coronaviruses is very promising, as their low toxicity and high surface performance make them superior among other nanomaterials; in conjugation with fluorescent probes they are promising semiconductor nanomaterials for the detection of various cellular processes and viral infections. In view of the successful results for inhibiting SARS-CoV-2, functional QDs could serve eminent role in the growth of safe nanotherapy for the cure of viral infections in the near future; their large surface areas help bind numerous molecules post-synthetically. Functionalized QDs with high functionality, targeted selectivity, stability and less cytotoxicity can be employed for highly sensitive co-delivery and imaging/diagnosis. Besides, due to the importance of safety and toxicity issues, QDs prepared from plant sources (e.g. curcumin) are much more attractive, as they provide good biocompatibility and low toxicity. In this review, the recent developments pertaining to the diagnostic and inhibitory potentials of QDs against SARS-CoV-2 are deliberated including important challenges and future outlooks. © 2022 Society of Chemical Industry (SCI).

5.
J Drug Deliv Sci Technol ; 67: 102899, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34630635

RESUMO

The inexorable coronavirus disease 2019 (COVID-19) pandemic with around 226 million people diagnosed and approximately 4.6 million deaths, is still moving toward more frightening statistics, calling for the urgent need to explore solutions for the current challenges in therapeutic and diagnostic approaches. The challenges associated with existing therapeutics in COVID-19 include lack of in vivo stability, efficacy, and safety. Nanoparticles (NPs) can offer a handful of tools to tackle these problems by enabling efficacious and safe delivery of both virus- and host-directed therapeutics. Furthermore, they can enable maximized clinical outcome while eliminating the chance of resistance to therapy by tissue-targeting and concomitant delivery of multiple therapeutics. The promising application of NPs as vaccine platforms is reflected by the major advances in developing novel COVID-19 vaccines. Two of the most critical COVID-19 vaccines are mRNA-based vaccines delivered via NPs, making them the first FDA-approved mRNA vaccines. Besides, NPs have been deployed as simple, rapid, and precise tools for point of care disease diagnosis. Not enough said NPs can also be exploited in novel ways to expedite the drug discovery process. In light of the above, this review discusses how NPs can overcome the hurdles associated with therapeutic and diagnostic approaches against COVID-19.

6.
Bioconjug Chem ; 32(8): 1875-1887, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34278778

RESUMO

Safe and efficient delivery of CRISPR/Cas9 systems is still a challenge. Here we report the development of fluorescent nitrogen- and zinc-doped carbon dots (N-Zn-doped CDs) using one-step microwave-aided pyrolysis based on citric acid, branched PEI25k, and different zinc salts. These versatile nanovectors with a quantum yield of around 60% could not only transfect large CRISPR plasmids (∼9 kb) with higher efficiency (80%) compared to PEI25k and lipofectamine 2000 (Lipo 2K), but they also delivered mRNA into HEK 293T cells with the efficiency 20 times greater than and equal to that of PEI25k and Lipo 2K, respectively. Unlike PEI25k, N-Zn-doped CDs exhibited good transfection efficiency even at low plasmid doses and in the presence of 10% fetal bovine serum (FBS). Moreover, these nanovectors demonstrated excellent efficiency in GFP gene disruption by transferring plasmid encoding Cas9 and sgRNA targeting GFP as well as Cas9/sgRNA ribonucleoproteins into HEK 293T-GFP cells. Hence, N-Zn-doped CDs with remarkable photoluminescence properties and high transfection efficiency in the delivery of both CRISPR complexes and mRNA provide a promising platform for developing safe, efficient, and traceable delivery systems for biological research.


Assuntos
Sistemas CRISPR-Cas , Carbono/química , Nitrogênio/química , Pontos Quânticos , RNA Mensageiro , Zinco/química , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Corantes Fluorescentes , Edição de Genes , Terapia Genética/métodos , Células HEK293 , Humanos , Plasmídeos/química , Soroalbumina Bovina
7.
Nanomedicine ; 32: 102331, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33181272

RESUMO

AgNPs@Chitosan and Co3O4-NPs@Chitosan were fabricated with Salvia hispanica. Results showed MZI values of 5 and 30 mm for Co3O4-NPs- and AgNPs@Chitosan against S. aureus, and 15 and 21 mm for Co3O4-NPs- and AgNPs@Chitosan against E. coli (24 h, 20 µg/mL), respectively. MTT assays showed up to 80% and 90%, 71% and 75%, and 91% and 94% mammalian cell viability for the green synthesized, chemically synthesized AgNPs and green synthesized AgNPs@Chitosan for HEK-293 and PC12 cells, respectively, and 70% and 71%, 59% and 62%, and 88% and 73% for the related Co3O4-NPs (24 h, 20 µg/mL). The photocatalytic activities showed dye degradation after 135 and 105 min for AgNPs@Chitosan and Co3O4-NPs@Chitosan, respectively. FESEM results showed differences in particle sizes (32 ±â€¯3.0 nm for the AgNPs and 41 ±â€¯3.0 nm for the Co3O4NPs) but AFM results showed lower roughness of the AgNPs@Chitosan (7.639 ±â€¯0.85 nm) compared to Co3O4NPs@Chitosan (9.218 ±â€¯0.93 nm), which resulted in potential biomedical applications.


Assuntos
Tecnologia Biomédica , Quitosana/química , Cobalto/química , Química Verde , Luz , Nanopartículas Metálicas/química , Óxidos/química , Prata/química , Animais , Antibacterianos/farmacologia , Catálise , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Concentração Inibidora 50 , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Células PC12 , Ratos , Salvia hispanica/química , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios X
8.
Nanotechnology ; 31(42): 425101, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32604076

RESUMO

This study, for the first time, reports the synthesis of CuO- and Cu2O nanoparticles (NPs) using the Salvia hispanica extract by a high-gravity technique. The original green synthesis procedure led to the formation of nanoparticles with promising catalytic and biological properties. The synthesized nanoparticles were fully characterized and their catalytic activity was evaluated through a typical Azide-Alkyne Cycloaddition (AAC) reaction. The potential antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacteria were investigated. It was shown that the antibacterial properties were independent of the NP morphology as well as of the texture of the synthesis media. As a result, the presently synthesized nanoparticles showed very good photocatalytic and catalytic activities in comparison with the literature. From a biological perspective, they showed lower cytotoxicity in comparison with the literature, and also showed higher antioxidant and antibacterial activities. Thus, these present green CuO and Cu2O nanoparticles deserve further attention to improve numerous medical applications.

9.
Eur J Clin Pharmacol ; 76(6): 765-773, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32266480

RESUMO

PURPOSE: Tocilizumab, a monoclonal antibody directed against the IL-6 receptor, might block detrimental effects of IL-6 on transplantation. IL-6 plays a considerable role in cytokine storm after stem cell transplantation as well as graft versus host disease, and it has also been shown to be involved in solid organ allograft rejection; therefore, tocilizumab is expected to promote graft survival. Nonetheless, due to the small number of studies and disparate methods of drug administration and outcome evaluation, for which types of transplantation, at which stages, and to what extent tocilizumab could be applied remains to be defined. METHODS: The Pubmed, SCOPUS and Google Scholar search engines were used to collect data. The keywords were determined by Pubmed MeSH. No time limitation was set and all types of articles were allowed.  RESULTS: According to the potential of Tocilozumab in controlling both cellular and humoral immunity it could be considered as a promising agent in tolerance induction; however, blocking IL-6 signaling might result in augmented infection rate in recipients. CONCLUSION: The need for providing effective and safe immunosuppressive agents to protect transplanted cells and organs against allo-reactivity urges the collection and discussion of all available findings about inhibition of determining immune components including cytokines; herein, we have summarized the clinical consequences of blocking IL-6 by tocilizumab in stem cell and solid organ transplantations.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Transplante de Órgãos , Receptores de Interleucina-6/antagonistas & inibidores , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro , Humanos , Imunossupressores , Receptores de Interleucina-6/metabolismo
10.
Inj Prev ; 26(Supp 1): i46-i56, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31915274

RESUMO

BACKGROUND: The global burden of road injuries is known to follow complex geographical, temporal and demographic patterns. While health loss from road injuries is a major topic of global importance, there has been no recent comprehensive assessment that includes estimates for every age group, sex and country over recent years. METHODS: We used results from the Global Burden of Disease (GBD) 2017 study to report incidence, prevalence, years lived with disability, deaths, years of life lost and disability-adjusted life years for all locations in the GBD 2017 hierarchy from 1990 to 2017 for road injuries. Second, we measured mortality-to-incidence ratios by location. Third, we assessed the distribution of the natures of injury (eg, traumatic brain injury) that result from each road injury. RESULTS: Globally, 1 243 068 (95% uncertainty interval 1 191 889 to 1 276 940) people died from road injuries in 2017 out of 54 192 330 (47 381 583 to 61 645 891) new cases of road injuries. Age-standardised incidence rates of road injuries increased between 1990 and 2017, while mortality rates decreased. Regionally, age-standardised mortality rates decreased in all but two regions, South Asia and Southern Latin America, where rates did not change significantly. Nine of 21 GBD regions experienced significant increases in age-standardised incidence rates, while 10 experienced significant decreases and two experienced no significant change. CONCLUSIONS: While road injury mortality has improved in recent decades, there are worsening rates of incidence and significant geographical heterogeneity. These findings indicate that more research is needed to better understand how road injuries can be prevented.


Assuntos
Carga Global da Doença , Saúde Global , Ferimentos e Lesões , Acidentes de Trânsito , Ásia , Humanos , Morbidade , Mortalidade/tendências , Anos de Vida Ajustados por Qualidade de Vida , Ferimentos e Lesões/mortalidade
11.
Nanomedicine ; 30: 102297, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32931927

RESUMO

This study investigated the synthesis of Pd nanoparticles (NPs) using a high-gravity technique mediated by Salvia hispanica leaf extracts. Biological assays confirmed their antibacterial activity against gram positive (S. aureus) and gram negative (E. coli) bacteria with significant antioxidant activity in comparison with the standards as well as low cellular toxicity on PC12 and HEK293 cell lines. To the best of our knowledge, this study can be considered as the first investigation of Pd-NPs synthesized by Salvia hispanica leaf extracts assisted by a high-gravity technique. In addition, the mentioned green synthesis procedure led to the formation of nanoparticles with considerable antibacterial properties independent of the morphology and texture of the green media of these nanoparticles. Considering the increasing rate of antimicrobial resistant bacteria deaths worldwide, this study introduces a novel green synthesis method and non-antibiotic nanoparticle which should be studied for a wide range of medical applications.


Assuntos
Gravitação , Química Verde , Nanopartículas Metálicas/química , Nanomedicina , Paládio/química , Animais , Escherichia coli/efeitos dos fármacos , Células HEK293 , Humanos , Testes de Sensibilidade Microbiana , Células PC12 , Extratos Vegetais/farmacologia , Ratos , Salvia/química , Staphylococcus aureus/efeitos dos fármacos
12.
Int J Mol Sci ; 21(14)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698479

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019. More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment. Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people. Considerable efforts are also directed at detecting and preventing different modes of community transmission. Among them is the rapid detection of virus presence on different surfaces with which people may come in contact. Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces. Nanomaterial-based methods are proven suitable for rapid detection. Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions. In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods. Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Estruturas Metalorgânicas/química , Nanotecnologia/métodos , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , COVID-19 , Genoma Viral/genética , Humanos , Nanopartículas Metálicas/química , Pandemias , RNA Viral/genética , SARS-CoV-2 , Sequenciamento Completo do Genoma
13.
J Cell Physiol ; 234(10): 16913-16924, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30809802

RESUMO

Significant advances have been achieved in recent years to ameliorate rheumatoid arthritis (RA) in animal models using gene therapy approaches rather than biological treatments. Although biological agents serve as antirheumatic drugs with suppressing proinflammatory cytokine activities, they are usually accompanied by systemic immune suppression resulting from continuous or high systemic dose injections of biological agents. Therefore, gene transfer approaches have opened an interesting perspective to deliver one or multiple genes in a target-specific or inducible manner for the sustained intra-articular expression of therapeutic products. Accordingly, many studies have focused on gene transferring methods in animal models by using one of the available approaches. In this study, the important strategies used to select effective genes for RA gene therapy have been outlined. Given the work done in this field, the future looks bright for gene therapy as a new method in the clinical treatment of autoimmune diseases such as RA, and by ongoing efforts in this field, we hope to achieve feasible, safe, and effective treatment methods.


Assuntos
Artrite Reumatoide/terapia , Terapia Genética , Artrite Reumatoide/genética , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica , Vetores Genéticos , Humanos , Vírus
14.
Nanotechnology ; 30(13): 135101, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30609415

RESUMO

Gene therapy using clustered regularly interspaced short palindromic repeat plasmids (pCRISPR) reduces mistakes in gene editing and prevents engendering integrational mutagenesis that has been seen in available genome engineering technologies. Developing an ideal and traceable nanocarrier, which can accurately and efficiently transfer this complex into the cytosol and which facilitates the journey towards the nucleus, is a fascinating area of research. Polyethylenimine (PEI) functionalized carbon dots (CD-PEI) were fabricated by one-step microwave assisted pyrolysis with an average size around 3 nm. This CD-PEI showed good potential for intracellular delivery of genetic materials (∼70%). Also, this CD-PEI with passive surface modification with low molecular PEI (2 kDa) has a very high quantum yield, as high as 40% with low cytotoxicity. The expression rate of the pCRISPR was around 15% in the HEK-293 cell which is comparable with the pristine PEI. Furthermore, the CD-PEI demonstrated good properties, such as high quantum yield, biocompatibility and tunable emission wavelengths, suggesting the potential application of photoluminescent functionalized CDs as a suitable, traceable nanocarrier for CRISPR delivery.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Portadores de Fármacos/síntese química , Pontos Quânticos/química , Carbono/química , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Terapia Genética , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos
15.
Arch Pharm (Weinheim) ; 348(5): 330-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25787800

RESUMO

A novel series of N-(2-(piperazin-1-yl)phenyl)aryl carboxamide derivatives were simply synthesized by Ugi-multicomponent reaction as ß-secretase (BACE1) inhibitors. The BACE1 inhibitory activity of the synthesized compounds was examined using a Forester resonance energy transfer (FRET)-based assay. Among the tested compounds, the N-(5-bromo-2-(4-phenylpiperazine-1-yl)phenyl)thiophene-carboxamide derivative 14 containing the N-cyclohexyl indole acetamide moiety showed superior BACE1 inhibition at 10 and 40 µM. The results of the molecular docking study indicated that compound 14 establishes favorable hydrogen bonding interactions with the catalytic amino acid residues Asp228 and Thr72 and could be well accommodated in the flap region and P2 and P'2 pockets of the BACE1 active site.


Assuntos
Amidas/farmacologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Piperazinas/farmacologia , Inibidores de Proteases/farmacologia , Amidas/síntese química , Amidas/metabolismo , Secretases da Proteína Precursora do Amiloide/química , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/química , Ácido Aspártico Endopeptidases/metabolismo , Sítios de Ligação , Domínio Catalítico , Desenho Assistido por Computador , Desenho de Fármacos , Transferência Ressonante de Energia de Fluorescência , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Piperazinas/síntese química , Piperazinas/metabolismo , Inibidores de Proteases/síntese química , Inibidores de Proteases/metabolismo , Conformação Proteica , Relação Estrutura-Atividade
16.
Front Bioeng Biotechnol ; 12: 1352717, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605986

RESUMO

This study developed a new burn wound dressing based on core-shell nanofibers that co-deliver antibiotic and antioxidant drugs. For this purpose, poly(ethylene oxide) (PEO)-chitosan (CS)/poly(D,L-lactide-co-glycolide) (PLGA) core-shell nanofibers were fabricated through co-axial electrospinning technique. Antibiotic levofloxacin (LEV) and antioxidant quercetin (QS) were incorporated into the core and shell parts of PEO-CS/PLGA nanofibers, respectively. The drugs could bond to the polymer chains through hydrogen bonding, leading to their steady release for 168 h. An in vitro drug release study showed a burst effect followed by sustained release of LEV and QS from the nanofibers due to the Fickian diffusion. The NIH 3T3 fibroblast cell viability of the drug loaded core-shell nanofibers was comparable to that in the control (tissue culture polystyrene) implying biocompatibility of the nanofibers and their cell supportive role. However, there was no significant difference in cell viability between the drug loaded and drug free core-shell nanofibers. According to in vivo experiments, PEO-CS-LEV/PLGA-QS core-shell nanofibers could accelerate the healing process of a burn wound compared to a sterile gauze. Thanks to the synergistic therapeutic effect of LEV and QS, a significantly higher wound closure rate was recorded for the drug loaded core-shell nanofibrous dressing than the drug free nanofibers and control. Conclusively, PEO-CS-LEV/PLGA-QS core-shell nanofibers were shown to be a promising wound healing material that could drive the healing cascade through local co-delivery of LEV and QS to burn wounds.

17.
Biomater Adv ; 158: 213771, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38271801

RESUMO

The efficacy of injectable micellar carriers is hindered due to the disassembly of micelles into free surfactants in the body, resulting in their dilution below the critical micelle concentration (CMC). Copolymer micelles were developed to address this issue, containing a superhydrophilic zwitterionic block and a superhydrophobic block with a disulfide bond, which exhibited a CMC lower than conventional micellar carriers. Cleavable copolymers composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) zwitterion and polycaprolactone CHLZW as the shell, with gold nanoparticles as their core, were studied to deliver doxorubicin to tumor cells while reducing the side effect of the free cytotoxic agent. The research focused on the impact of gold nanoparticles present in targeted TMT-micelles core on stability and in vivo bioavailability and sonotoxicity of the nanoparticles, as well as their synergistic effect on targeted chemotherapy. The nanomicelles prepared in this study demonstrated excellent biocompatibility and responsiveness to stimuli. PCL-SS-MPC nanomicelles displayed drug release in response to GSH and pH, resulting in high DOX release at GSH 10 mM and pH 5. Our findings, supported by MTT, flow cytometry, and confocal laser scanning microscopy, demonstrated that AuS-PM-TMTM-DOX micelles effectively induced apoptosis and enhanced cellular uptake in MCF7 and MDA-MB231 cell lines. The cytotoxic effects of AuS-PM-DOX/US on cancer cells were approximately 38 % higher compared to AuS-PM-DOX samples at a concentration of IC50 0.68 nM. This increase in cellular toxicity was primarily attributed to the promotion of apoptosis. The introduction of disulfide linkages in AuSNPs resulted in increased ROS production when exposed to ultrasound stimulation, due to a reduction in GSH levels. Compared to other commercially available nanosensitizers such as titanium dioxide, exposure of AuS-PM to ultrasound radiation (1.0 W/cm, 2 min) significantly enhanced cavitation effects and resulted in 3 to 5 times higher ROS production. Furthermore, laboratory experiments using human breast cancer cells (MDA-MB-231, MCF7) demonstrated that the toxicity of AuS-PM in response to ultrasound waves is dose-dependent. The findings of this study suggest that this formulated nanocarrier holds great potential as a viable treatment option for breast cancer. It can induce apoptosis in cancer cells, reduce tumor size, and display notable therapeutic efficacy.


Assuntos
Antineoplásicos , Neoplasias da Mama , Nanopartículas Metálicas , Humanos , Feminino , Micelas , Neoplasias da Mama/tratamento farmacológico , Ouro , Espécies Reativas de Oxigênio , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Antineoplásicos/farmacologia , Polímeros , Oxirredução , Concentração de Íons de Hidrogênio , Dissulfetos
18.
ACS Omega ; 9(1): 1183-1195, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222665

RESUMO

Biocompatible and bioactive carbon-based nanocomposites are ingeniously designed and fabricated with the aim of enhancing drug delivery applicability in breast cancer treatment. Reduced graphene oxide (rGO) and multiwalled carbon nanotubes (MWCNTs) are utilized as nanocarriers for increasing penetrability into cells and the loading capacity. What sets our study apart is the strategic incorporation of the two different complexes of silver (AgL2) and palladium (PdL2) with the carboxamide-based ligand C9H7N3OS (L), which have been synthesized and decorated on nanocarriers alongside doxorubicin (DOX) for stabilizing DOX by π-π interactions and hydrogen bonding. Although DOX is a well-known cancer therapy agent, the efficacy of DOX is hindered owing to drug resistance, poor internalization, and limited site specificity. Aside from stabilizing DOX on nanocarriers, our carbon-based nanocarriers are tailored to act as a precision-guided missile, strategically by adorning with target-sensitive complexes. Based on the literature, carboxamide ligands can connect to overexpressed receptors on cancerous cells and inhibit them from proliferation signaling. Also, the complexes have an antibacterial activity that can control the infection caused by decreasing white blood cells and necrosis of cancerous cells. A high-concentration cytotoxicity assay revealed that decorating PdL2 on a DOX-containing nanocarrier not only increased cytotoxicity to breast cancerous cell lines (MDA-MB-231 and MCF-7) but also revealed higher cell viability on a normal cell line (MCF-10A). The drug release screening results showed that the presence of PdL2 led to 72 h correlate release behavior in acidic and physiological pH profiles, while the AgL2-containing nanocomposite showed an analogue behavior for just 6 h and the release of DOX continued and after about 100 h hit the top.

19.
Int J Biol Macromol ; 249: 126705, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37673162

RESUMO

A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.


Assuntos
Nanofibras , Masculino , Ratos , Animais , Ratos Wistar , Celulose
20.
ACS Pharmacol Transl Sci ; 6(12): 1758-1779, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38093832

RESUMO

Personalized medicine is a new approach toward safer and even cheaper treatments with minimal side effects and toxicity. Planning a therapy based on individual properties causes an effective result in a patient's treatment, especially in a complex disease such as cancer. The benefits of personalized medicine include not only early diagnosis with high accuracy but also a more appropriate and effective therapeutic approach based on the unique clinical, genetic, and epigenetic features and biomarker profiles of a specific patient's disease. In order to achieve personalized cancer therapy, understanding cancer biology plays an important role. One of the crucial applications of personalized medicine that has gained consideration more recently due to its capability in developing disease therapy is related to the field of stem cells. We review various applications of pluripotent, somatic, and cancer stem cells in personalized medicine, including targeted cancer therapy, cancer modeling, diagnostics, and drug screening. CRISPR-Cas gene-editing technology is then discussed as a state-of-the-art biotechnological advance with substantial impacts on medical and therapeutic applications. As part of this section, the role of CRISPR-Cas genome editing in recent cancer studies is reviewed as a further example of personalized medicine application.

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