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1.
Sci Rep ; 14(1): 21325, 2024 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266594

RESUMEN

The synthesis and characterization of metal complexes have garnered significant attention due to their versatile applications in scientific and biomedical fields. In this research, two novel copper (Cu) complexes, [Cu(L)(L')(H2O)2] (1) and [Cu(L)(Im)H2O] (2), where L = pyridine-2,6-dicarboxylic acid, L' = 2,4-diamino-6-hydroxypyrimidine, and Im = imidazole, were investigated concerning their sonochemical synthesis, spectroscopic analysis, and biological activity. The complexes' structural characterization was achieved using analytical techniques, including single-crystal X-ray structure determination, FTIR, PXRD, TGA and DTA, SEM, TEM, and EDS. Complex (1) displayed a six-coordinated Cu2+ ion, while complex (2) exhibited a five-coordinated Cu2+ ion. The crystal structures revealed monoclinic (C2/c) and triclinic (P-1) space groups, respectively. Both complexes showcased zero-dimensional (0D) supramolecular networks, primarily driven by hydrogen bonding and π-π stacking interactions, which played pivotal roles in stabilizing the structures and shaping the unique supramolecular architecture. Both complexes demonstrated significant antioxidant activity, suggesting their capability to neutralize free radicals and mitigate oxidative stress-related diseases. Hemolysis percentages were less than 2%, per the ASTM F756-00 standard, indicating non-hemolytic behavior. Low cytotoxicity was observed against fibroblast and MCF-7 cell lines. They do not exhibit antibacterial activity against Escherichia coli and Staphylococcus aureus. These findings suggest that the synthesized Cu2+‒complexes hold considerable promise for applications in drug delivery and cancer treatment. This research contributes to the advancement of supramolecular chemistry and the development of multifunctional materials for diverse scientific and medical applications.


Asunto(s)
Complejos de Coordinación , Cobre , Cobre/química , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Cristalografía por Rayos X , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Células MCF-7 , Hemólisis/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química
2.
Sci Rep ; 14(1): 6398, 2024 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-38493249

RESUMEN

This study investigates the probiotic and anti-cancer effects of 21 isolated Lactobacillus strains from cheese, milk, and yogurt in Kermanshah, Iran, on oral cancer cell lines KB and OSCC. Four selected isolates (Y33, M45, C5, and C28) displayed good viability and resistance to specific antibiotics. Notably, strains C28 and Y33 exhibited the best results, showing susceptibility or semi-susceptibility to five antibiotics. Y33, with high cell surface hydrophobicity (62%), demonstrated significant anti-pathogenic activity, inhibiting the growth of tested pathogens and displaying strong adhesion to human intestinal Caco-2 cells (52%). Further assessments, including acridine orange/ethidium bromide staining and mRNA expression analysis, revealed four isolates (C5, C28, M45, and Y33) with promising probiotic properties. Particularly, Y33's protein-based extract metabolites showed dose- and time-dependent inhibition of KB and OSCC cancer cell lines, inducing apoptosis without significant cytotoxic effects on normal cells. Y33 (Lactiplantibacillus plantarum) exhibited the strongest probiotic potential, surpassing conventional anti-cancer drugs, suggesting its therapeutic potential for preventing oral cancer cell proliferation and improving survival rates in oral cancer patients.


Asunto(s)
Queso , Neoplasias de la Boca , Probióticos , Humanos , Animales , Lactobacillus , Leche , Células CACO-2 , Yogur , Probióticos/farmacología , Antibacterianos/farmacología
3.
RSC Adv ; 13(49): 34587-34597, 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-38024994

RESUMEN

The anticancer properties of curcumin have been broadly examined in several shapes, such as nanoparticles and nanocomposite structures. Despite its benefits, curcumin also has some disadvantages, including rapid metabolism, poor absorption, and rapid systemic excretion. Therefore, numerous strategies have been used to increase curcumin's bioavailability. One of these approaches is the use of porous particles like aerogels as drug carriers. Aerogels are special due to their peculiar physical structure. They have a high specific surface area, a significant amount of porosity, and a solid composition, which make them a good choice for drug delivery systems. In the present study, a pH-sensitive aerogel was constructed and evaluated for targeted drug delivery of curcumin to colon cancer. To control the release of curcumin, trehalose was used as a coating agent, and PLP (poly(l-lysine isophthalamide)) was used as a targeted drug delivery agent. PLP is a pseudo-peptidic polymer that increases the cell permeability. In order to investigate and compare the synthesized aerogel before and after loading curcumin and coating with trehalose, physicochemical characterization analyses were performed. Finally, the efficacy of the final formulation was evaluated on HT29 colon cells using the cell bioavailability test. The results indicated the successful synthesis of the aerogel with porous structure with solitary cavities. The trehalose coating performed well, preventing drug release at lower pH but allowing the drug to be released at its intended site. The designed curcumin-loaded porous particles functionalized with PLP showed significant efficacy due to increasing penetration of curcumin into cells, and has potential for use as a new drug carrier with dual effectivity in cancer therapy.

4.
Int J Biol Macromol ; 253(Pt 6): 127214, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37797855

RESUMEN

A novel strategy was designed and developed based of horseradish peroxidase (HRP)-mediated crosslinking of tyramine-functionalized starch (Tyr-St), tannic acid (TA) and phenolated-magnetic nanoparticles (Fe3O4-PhOH NPs), and simultaneous loading of doxorubicin hydrochloride (Dox) to afford a pH-responsive magnetic hydrogel-based drug delivery system (DDS) for synergistic in vitro chemo/hyperthermia therapy of human breast cancer (MCF-7) cells. The developed St-g-PTA/Fe3O4 magnetic hydrogel showed porous micro-structure with saturation magnetization (δs) value of 19.2 emu g-1 for Fe3O4 NPs content of ∼7.4 wt%. The pore sizes of the St-g-PTA/Fe3O4 hydrogel was calculated to be 2400 ± 200 nm-2. In vitro drug release experiments exhibited the developed DDS has pH-dependent drug release behavior, while at physiological pH (7.4) released only 30 % of the loaded drug after 100 h. Human serum albumin (HSA) adsorption capacities of the synthesized St/Fe3O4 and St-g-PTA/Fe3O4 magnetic hydrogels were obtained as 86 ± 2.2 and 77 ± 1.9 µgmg-1, respectively. The well-known MTT-assay approved the cytocompatibility of the developed St-g-PTA/Fe3O4 hydrogel, while the Dox-loaded system exhibited higher anti-cancer activity than those of the free Dox as verified by MTT-assay, and optical as well as florescent microscopies imaging. The synergistic chemo/hyperthermia therapy effect was also verified for the developed St-g-PTA/Fe3O4-Dox via hot water approach.


Asunto(s)
Hipertermia Inducida , Neoplasias , Humanos , Hidrogeles , Almidón , Doxorrubicina/química , Hipertermia Inducida/métodos , Fenómenos Magnéticos , Liberación de Fármacos
5.
Eur J Med Chem ; 260: 115765, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37659194

RESUMEN

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases.


Asunto(s)
Descubrimiento de Drogas , Procesamiento Proteico-Postraduccional , Proteolisis , Fosforilación , Ubiquitinación , Quimera Dirigida a la Proteólisis
6.
Biomed Pharmacother ; 146: 112531, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34906771

RESUMEN

Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.


Asunto(s)
Berberina , Quitosano , Nanoestructuras , Antibacterianos/farmacología , Berberina/química , Disponibilidad Biológica , Quitosano/química
7.
ACS Chem Neurosci ; 12(24): 4475-4490, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34841846

RESUMEN

The blood-brain barrier (BBB) is considered as the most challenging barrier in brain drug delivery. Indeed, there is a definite link between the BBB integrity defects and central nervous systems (CNS) disorders, such as neurodegenerative diseases and brain cancers, increasing concerns in the contemporary era because of the inability of most therapeutic approaches. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have already been identified as having several advantages in facilitating the transportation of hydrophilic and hydrophobic agents across the BBB. This review first explains BBB functions and its challenges in brain drug delivery, followed by a brief description of nanoparticle-based drug delivery for brain diseases. A detailed presentation of recent progressions in optimizing SLNs and NLCs for controlled release drug delivery, gene therapy, targeted drug delivery, and diagnosis of neurodegenerative diseases and brain cancers is approached. Finally, the problems, challenges, and future perspectives in optimizing these carriers for potential clinical application were described briefly.


Asunto(s)
Barrera Hematoencefálica , Nanopartículas , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Lípidos , Liposomas
8.
Drug Dev Ind Pharm ; 47(7): 1166-1174, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34590962

RESUMEN

A dual stimuli-responsive magnetic nanohydrogel was fabricated as a potent drug delivery system (DDS) for 'smart' treatment of cancer by chemo/hyperthermia approach. For this objective, Fe3O4 nanoparticles (NPs) were produced via a co-precipitation approach and then modified by 3-(trimethoxysilyl) propylmethacrylate (MPS) moiety. The modified NPs were copolymerized with N,N'-(dimethylamino)ethyl methacrylate (DMAEMA), and maleic anhydride (MA) monomers by a free radical polymerization approach to afford a Fe3O4@P(DMAEMA-co-MA) core-shell NPs. Afterward, the NPs were shell crosslinked by the reaction of anhydride unites with neutralized cystamine (Cys). The fabricated pH- and reduction-responsive magnetic nanohydrogel was physically loaded with methotrexate (MTX), as an anticancer drug, and its drug loading efficiency (LE) was calculated as 64 ± 2.7%. The developed nanohydrogel/MTX exhibited proper stimuli-triggered drug release behavior that qualified it as an efficient DDS according to the abnormal micro-environment of cancerous tumors. The anticancer activity investigation using chemo/hyperthermia therapy approach by MTT-assay revealed that the nanohydrogel/MTX might show better clinical outcomes than those of the free MTX.


Asunto(s)
Antineoplásicos , Hipertermia Inducida , Nanopartículas , Doxorrubicina , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Fenómenos Magnéticos
9.
J Control Release ; 338: 341-357, 2021 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-34428480

RESUMEN

Microneedle arrays have recently received much attention as cancer detection and treatment platforms, because invasive injections and detection of the biopsy are not needed, and drug metabolism by the liver, as well as adverse effects of systemic drug administration, are diminished. Microneedles have been used for diagnosis, vaccination, and in targeted drug delivery of breast cancer. In this review, we summarize the recent progress in diagnosis and targeted drug delivery for breast cancer treatment, using microneedle arrays to deliver active molecules through the skin. The results not only suggest that health and well-being of patients are improved, but also that microneedle arrays can deliver anticancer compounds in a relatively noninvasive manner, based on body weight, breast tumor size, and circulation time of the drug. Moreover, microneedles could allow simultaneous loading of multiple drugs and enable controlled release, thus effectively optimizing or preventing drug-drug interactions. This review is designed to encourage the use of microneedles for diagnosis and treatment of breast cancer, by describing general properties of microneedles, materials used for construction, mechanism of action, and principal benefits. Ongoing challenges and future perspectives for the application of microneedle array systems in breast cancer detection and treatment are highlighted.


Asunto(s)
Neoplasias de la Mama , Administración Cutánea , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Humanos , Microinyecciones , Agujas , Piel/metabolismo
10.
Neurotox Res ; 39(5): 1589-1612, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34169405

RESUMEN

Neurodegenerative diseases such as stroke and Alzheimer's disease (AD) are two inter-related disorders that affect the neurons in the brain and central nervous system. Alzheimer's is a disease by undefined origin and causes. Stroke and its most common type, ischemic stroke (IS), occurs due to the blockade of cerebral blood vessels. As an important feature, both of disorders are associated with irreversible damages to the brain and nervous system. In this regard, finding common signaling pathways and the same molecular origin between these two diseases may be a promising way for their solution. On the basis of literature appraisal, the most common signaling cascades implicated in the pathogenesis of AD and stroke including notch, autophagy, inflammatory, and insulin signaling pathways were reviewed. Furthermore, current therapeutic strategies including natural and synthetic pharmaceuticals aiming modulation of respective signaling factors were scrutinized to ameliorate neural deficits in AD and stroke. Taken together, digging deeper in the common connections and signal targeting can be greatly helpful in understanding and unified treating of these disorders.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Animales , Autofagia/efectos de los fármacos , Autofagia/fisiología , Encéfalo/metabolismo , Encéfalo/patología , Humanos , Insulina/administración & dosificación , Transducción de Señal/fisiología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación
11.
J Adv Res ; 30: 171-184, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-34026294

RESUMEN

Background: Heterocyclic compounds have always been used as a core portion in the development of anticancer drugs. However, there is a pressing need for developing inexpensive and simple alternatives to high-cost and complex chemical agents-based catalysts for large-scale production of heterocyclic compounds. Also, development of some smart platforms for cancer treatment based on nanoparticles (NPs) which facilitate Fenton reaction have been widely explored by different scientists. Magnetic NPs not only can serve as catalysts in the synthesis of heterocyclic compounds with potential anticancer properties, but also are widely used as smart agents in targeting cancer cells and inducing Fenton reactions. Aim of Review: Therefore, in this review we aim to present an updated summary of the reports related to the main clinical or basic application and research progress of magnetic NPs in cancer as well as their application in the synthesis of heterocyclic compounds as potential anticancer drugs. Afterwards, specific tumor microenvironment (TME)-responsive magnetic nanocatalysts for cancer treatment through triggering Fenton-like reactions were surveyed. Finally, some ignored factors in the design of magnetic nanocatalysts- triggered Fenton-like reaction, challenges and future perspective of magnetic nanocatalysts-assisted synthesis of heterocyclic compounds and selective cancer therapy were discussed.Key Scientific Concepts of Review:This review may pave the way for well-organized translation of magnetic nanocatalysts in cancer therapy from the bench to the bedside.


Asunto(s)
Antineoplásicos/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/química , Catálisis , Humanos , Peróxido de Hidrógeno/química , Hipertermia Inducida/métodos , Hierro/química , Fenómenos Magnéticos , Ratones , Neoplasias/metabolismo , Fototerapia/métodos , Microambiente Tumoral/efectos de los fármacos
12.
J Control Release ; 333: 91-106, 2021 05 10.
Artículo en Inglés | MEDLINE | ID: mdl-33774120

RESUMEN

The bioprinting technique with specialized tissue production allows the study of biological, physiological, and behavioral changes of cancerous and non-cancerous tissues in response to pharmacological compounds in personalized medicine. To this end, to evaluate the efficacy of anticancer drugs before entering the clinical setting, tissue engineered 3D scaffolds containing breast cancer and derived from the especially patient, similar to the original tissue architecture, can potentially be used. Despite recent advances in the manufacturing of 3D bioprinted breast cancer tissue (BCT), many studies still suffer from reproducibility primarily because of the uncertainty of the materials used in the scaffolds and lack of printing methods. In this review, we present an overview of the breast cancer environment to optimize personalized treatment by examining and identifying the physiological and biological factors that mimic BCT. We also surveyed the materials and techniques related to 3D bioprinting, i.e, 3D bioprinting systems, current strategies for fabrication of 3D bioprinting tissues, cell adhesion and migration in 3D bioprinted BCT, and 3D bioprinted breast cancer metastasis models. Finally, we emphasized on the prospective future applications of 3D bioprinted cancer models for rapid and accurate drug screening in breast cancer.


Asunto(s)
Bioimpresión , Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Impresión Tridimensional , Estudios Prospectivos , Reproducibilidad de los Resultados , Ingeniería de Tejidos , Andamios del Tejido
13.
Carbohydr Polym ; 254: 117422, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33357903

RESUMEN

Chemotherapy as the main cancer treatment method has non-specific effects and various side-effects. Accordingly, significant attempts have been conducted to enhance its efficacy through design and development of "smart" drug delivery systems (DDSs). In this context, natural gums, as a nice gift by the nature, can be exploited as stimuli-responsive DDSs for cancer treatment in part due to their renewability, availability, low cost, bioactivity, biocompatibility, low immunogenicity, biodegradability, and acceptable stability in both in vitro and in vivo conditions. However, some shortcomings (e.g., poor mechanical properties and high hydration rate) restrict their biomedical application ranges that can be circumvented through modification process (e.g., grafting of stimuli-responsive polymers or small molecules) to obtain tailored biomaterials. This review article aimed to compile the stimuli-responsive DDSs based on natural gums. In addition, different types of stimuli, the fundamental features of natural gums, as well as their chemical modification approaches are also shortly highlighted.


Asunto(s)
Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos/métodos , Neoplasias/tratamiento farmacológico , Polisacáridos/química , Polímeros de Estímulo Receptivo/química , Plásticos Biodegradables/química , Humanos , Nanogeles/química
14.
Carbohydr Polym ; 252: 117229, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33183649

RESUMEN

A new strategy for design and development of a magnetic "smart" drug delivery system (DDS) based on ß-cyclodextrin (ß-CD) and poly(2-ethyl-2-oxazoline) (PEtOx) was reported. For this purpose, a ß-CD-(I)7 was acetylated, and then EtOx monomer was grafted onto the acetylated ß-CD-(I)7 through cationic ring-opening polymerization followed by simultaneous crosslinking with amine-end capped Fe3O4 nanoparticles (Fe3O4-NH2 NPs) and cystamine to produce a ß-CD-g-(PEtOx)7/Fe3O4 as a reduction- and pH-responsive magnetic DDS. The developed magnetic nanohydrogel was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies, as well as its pH- and reduction-triggered drug release behaviors were investigated. The anticancer activity of the formulated ß-CD-g-(PEtOx)7/Fe3O4-Dox was investigated against MCF7 cells. According to the results, the formulated ß-CD-g-(PEtOx)7/Fe3O4-Dox can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis due to its high drug loading value (∼ 74 %), slow and stimuli-triggered drug release behavior, and acceptable magnetic properties.


Asunto(s)
Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Hipertermia Inducida , Nanopartículas de Magnetita/química , Neoplasias/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Liberación de Fármacos , Humanos , Hidrogeles/uso terapéutico , Concentración de Iones de Hidrógeno , Células MCF-7 , Poliaminas/química , beta-Ciclodextrinas/química
15.
Sci Rep ; 10(1): 14569, 2020 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-32884004

RESUMEN

This scenario was designed to investigate the protein corona pattern on the pillar-layer surface of a Cu-based metal-organic framework (MOF) in human plasma. The [Cu(L)(L/)].1.3DMA (MOF-1) {L = 4, 4/-bipyridine and L/ = 5-aminoisophthalic acid}, was synthesized through the sonochemical irradiation approach as well as characterized by various techniques like scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction and single-crystal X-ray diffraction. The space group was determined to be an orthorhombic space group (Pbam) by single-crystal X-ray diffraction. Single-crystal X-ray analyses on MOF-1 showed that Cu+2 ion was 6-coordinated. Besides, to study and clarify interactions between MOFs and biological milieu, human whole blood plasma was selected as a model. Fluorescence spectroscopy and SDS-PAGE techniques were employed to explore quantitative and qualitative in situ characterization of protein corona as well. Furthermore, cell viability in a cancerous cell lines was evaluated by MTT assay in the presence and absence of the corona. The results from SDS-PAGE illustrated that the most adsorbed quantity among plasma proteins belongs to fibrinogen (α, ß and γ chains), and this protein showed the maximum frequency on the MOF-1s surface, so the possible interactions of MOF-1s with fibrinogen also studied using fluorescence spectroscopy and corresponding data were plotted. According to the obtained data from MTT assay, these structures have concentration-dependent toxicity. In brief, based on the obtained data in the current study, the designed MOF can be introduced as a new desirable carrier for drug/gen delivery after further prerequisite assessments.


Asunto(s)
Neoplasias de la Mama/patología , Proliferación Celular , Estructuras Metalorgánicas/farmacología , Corona de Proteínas/química , Albúmina Sérica Humana/farmacología , Seroglobulinas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Células MCF-7 , Estructuras Metalorgánicas/química
16.
Drug Dev Ind Pharm ; 46(11): 1832-1843, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32897756

RESUMEN

A novel multi-stimuli-responsive theranostic nanomedicine was designed and fabricated by the conjugation of a thiol end-capped poly(N-isopropylacrylamide-block-acrylic acid) (HS-PNIPAAm-b-PAA) onto Fe3O4@Au nanoparticles (NPs) followed by physical loading of doxorubicin hydrochloride (Dox) as a general anticancer drug. For this purpose, Fe3O4@Au NPs were fabricated through small Au nanolayer grown on larger magnetic NPs. A HS-PNIPAAm-b-PAA was synthesized through an atom transfer radical polymerization (ATRP) approach, and then conjugated with as-synthesized Fe3O4@Au NPs by Au-S bonding. The Dox loading capacity of the synthesized Fe3O4@Au/Polymer theranostic NPs was calculated to be 81%. The theranostic nanomedicine exhibited excellent in vitro drug release behavior under pH and thermal stimuli. The anticancer activity evaluation using MTT assay (against MCF7 cells) revealed that the fabricated Fe3O4@Au/Polymer has high potential as theranostic nanomedicine for cancer therapy of solid tumors. This nanosystem can also applied in photothermal therapy, hyperthermia therapy, and their combination with chemotherapy due to presence of gold and Fe3O4 nanomaterials in its structure.


Asunto(s)
Hipertermia Inducida , Nanopartículas del Metal , Nanopartículas , Neoplasias , Doxorrubicina/química , Doxorrubicina/farmacología , Oro , Humanos , Neoplasias/tratamiento farmacológico , Nanomedicina Teranóstica
17.
Int J Biol Macromol ; 156: 438-445, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32298719

RESUMEN

This study aimed to design and development of a magnetic natural hydrogel based on alginate (Alg), gelatin (Gel), and Fe3O4 magnetic nanoparticles (MNPs) as an efficient and "smart" drug delivery system (DDS) for cancer therapy. First, Alg was partially oxidized (OAlg), and then the Alg-Gel chemical hydrogel was synthesized through "Shift-Base" condensation reaction. Afterward, Fe3O4 NPs were incorporated into the hydrogel through in situ chemical co-precipitation approach. The scanning electron microscopy (SEM) image exhibited that the fabricated Alg-Gel hydrogel has porous microstructure without microphase separation. Transmission electron microscopy (TEM) revealed the well-defined formation of Fe3O4 NPs throughout the Alg-Gel hydrogel with spherical shapes in the size range of 25 ± 10 nm. Saturation magnetization (δs) value of the Alg-Gel/Fe3O4 was obtained to be 31 emu g-1 that represent proper magnetic property for "smart" drug delivery purposes. The obtained Alg-Gel/Fe3O4 was loaded with doxorubicin hydrochloride (Dox), and its drug loading and encapsulation efficiencies as well as its anticancer activity was investigated against Hela cells. The formulated Alg-Gel/Fe3O4-Dox exhibited pH-dependent drug release behavior due to presence of carboxylic acid groups in the DDS. According to the results, the Alg-Gel/Fe3O4 magnetic hydrogel can be considered as an efficient and "smart" DDS for cancer therapy and diagnosis.


Asunto(s)
Alginatos/química , Antineoplásicos/administración & dosificación , Productos Biológicos/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Gelatina/química , Hidrogeles/química , Antineoplásicos/farmacología , Técnicas de Química Sintética , Composición de Medicamentos , Liberación de Fármacos , Humanos , Nanopartículas Magnéticas de Óxido de Hierro/química , Nanopartículas Magnéticas de Óxido de Hierro/ultraestructura , Estructura Molecular
18.
Int J Biol Macromol ; 154: 795-817, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32198035

RESUMEN

Despite the recent advances in the treatment strategies of peripheral nerve system defects, peripheral nerve injury (PNI) is still one of the most important health issues with increasing incidence worldwide. The most commonly used treatment approaches are allografts, xenografts, and autologous, which have some drawbacks, including complications, limited source of the donor tissue, tubular collapse, and scar tissue formation. In this context, regenerative medicine has been introduced as a powerful approach to improve the healing process and obtain acceptable functional recovery in the injury site using living cells, scaffold, and bioactive (macro-) molecules. Amongst them, scaffold as a three-dimensional (3D) support biomaterial, structurally bridged the gap or site of injury in order to provide physical and chemical cues to promote correct reinnervation and functional regeneration. Amongst different scaffolding biomaterials, naturally occurring biological macromolecules (more especially proteins and polysaccharides)-based hydrogels exhibited promising results due to their fascinating physicochemical, as well as physiologically relevant properties. This review highlights the recent progress in the development of natural hydrogels-based neural scaffolds. Furthermore, PNI healing process, current status, and challenges are also shortly discussed.


Asunto(s)
Materiales Biocompatibles/uso terapéutico , Hidrogeles/uso terapéutico , Péptidos/uso terapéutico , Traumatismos de los Nervios Periféricos/terapia , Polisacáridos/uso terapéutico , Ingeniería de Tejidos , Animales , Humanos , Regeneración Nerviosa , Andamios del Tejido
19.
Nanoscale ; 12(8): 4935-4944, 2020 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-32051994

RESUMEN

It is becoming increasingly accepted that various diseases have a capacity to alter the composition of plasma proteins. This alteration in protein composition may consequently change the targeting capacity of nanoparticles (NPs). In this study, the impact of a model targeting ligand's (i.e., Transferrin; Tf) concentration in human plasma on the targeting capacity of gold NPs (Au NPs), pre-conjugated with Tf, is investigated. Our findings demonstrate that the protein corona formation by both healthy and Tf depleted human plasma diminishes the targeting efficacy of Au NPs within human cancer cells despite a preservation of targeting ability by plasma with excess Tf (10-fold). Moreover, the plasma samples obtained from patients with various Tf levels (e.g., thalassemia major, sickle cell anemia, aplastic anemia, and iron deficiency anemia) have affected the accessibility of the targeting Tf in the corona layer and subsequently affected their targeting ability, which emphasizes the critical role of disease-specific protein corona on the efficacy of Au NPs. Ultimately, variations of protein concentration (e.g., due to disease occurrence and progress) in plasma affect its recruiting in corona formation, and in turn, affect the targeting and therapeutic efficacies of Au NPs.


Asunto(s)
Sistemas de Liberación de Medicamentos , Oro/química , Nanopartículas del Metal/química , Plasma/química , Corona de Proteínas/química , Transferrina/química , Humanos
20.
J Alzheimers Dis ; 59(4): 1187-1202, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28759965

RESUMEN

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.


Asunto(s)
Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Nanopartículas del Metal/química , Esclerosis Múltiple/sangre , Esclerosis Múltiple/diagnóstico , Corona de Proteínas/metabolismo , Ácido Cítrico , Colorimetría , Cisteamina , Femenino , Oro , Humanos , Masculino , Polietilenglicoles , Sensibilidad y Especificidad , Espectrometría de Fluorescencia
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