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1.
J Phys Chem B ; 128(25): 6151-6166, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38845485

RESUMO

This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (ηrel) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (ΔG°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.


Assuntos
Micelas , Poloxâmero , Polietilenoglicóis , Poloxâmero/química , Polietilenoglicóis/química , Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Humanos , Propilenoglicóis/química , Viscosidade , Simulação de Dinâmica Molecular
2.
Biomater Sci ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832912

RESUMO

The field of biomaterials is a continuously evolving interdisciplinary field encompassing biological sciences, materials sciences, chemical sciences, and physical sciences with a multitude of applications realized every year. However, different biomaterials developed for different applications have unique challenges in the form of biological barriers, and addressing these challenges simultaneously is also a challenge. Nevertheless, immense progress has been made through the development of novel materials with minimal adverse effects such as DNA nanostructures, specific synthesis strategies based on supramolecular chemistry, and modulating the shortcomings of existing biomaterials through effective functionalization techniques. This review discusses all these aspects of biomaterials, including the challenges at each level of their development and application, proposed countermeasures for these challenges, and some future directions that may have potential benefits.

3.
ACS Appl Bio Mater ; 7(6): 3915-3931, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38836645

RESUMO

One of the crucial requirements of quantum dots for biological applications is their surface modification for very specific and enhanced biological recognition and uptake. Toward this end, we present the green synthesis of bright, red-emitting carbon quantum dots derived from mango leaf extract (mQDs). These mQDs are conjugated electrostatically with dopamine to form mQDs-dopamine (mQDs:DOPA) bioconjugates. Bright-red fluorescence of mQDs was used for bioimaging and uptake in cancerous and noncancerous cell lines, tissues, and in vivo models like zebrafish. mQDs exhibited the highest uptake in brain tissue compared to the heart, kidney, and liver. mQD:DOPA conjugates killed breast cancer cells and increased uptake in epithelial RPE-1 cells and zebrafish. Additionally, mQDs:DOPA promoted neuronal differentiation of SH-SY5Y cells to differentiated neurons. Both mQDs and mQDs:DOPA exhibited the potential for higher collective cell migrations, implicating their future potential as next-generation tools for advanced biological and biomedical applications.


Assuntos
Carbono , Diferenciação Celular , Dopamina , Pontos Quânticos , Peixe-Zebra , Pontos Quânticos/química , Humanos , Carbono/química , Carbono/farmacologia , Dopamina/metabolismo , Dopamina/química , Animais , Diferenciação Celular/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Tamanho da Partícula , Teste de Materiais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Imagem Óptica , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral
4.
Biomater Adv ; 161: 213886, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38735200

RESUMO

Altering the route of uptake by the cells is an attractive strategy to overcome drug-receptor adaptation problems. Carbon nanoparticles (CNPs) with emission beyond tissue autofluorescence for imaging biological tissues were used to study the phenomenon of uptake by the cells. In this regard, red-emitting carbon nanoparticles (CNPs) were synthesized and incorporated onto lipid microbubbles (MBs). The CNPs showed red emissions in the range of 640 nm upon excitation with 480 nm wavelength of light. Atomic force microscopic and confocal microscopic images showed the successful loading of CNPs onto the MB. Carbon nanoparticle loaded microbubbles (CNP-MBs) were treated with NIH 3 T3 cells at different concentrations. Confocal microscopic imaging studies confirm the presence of CNPs inside the treated cells. Cytotoxicity studies revealed that the CNPs showed minimal toxicity towards cells after loading onto MBs. The CNPs are usually taken up by the cells through the clathrin-mediated (CME) pathway, but when loaded onto MBs, the mechanism of uptake of CNPs is altered, and the uptake by the cells was observed even in the presence of inhibitors for the CME pathway. Loading CNPs onto MBs resulted in the uptake of CNPs by the cell through micropinocytosis and sonophoresis in the presence of ultrasound. The in vivo uptake CNP-MBs were performed in Danio rerio (Zebrafish larvae). This study provides insights into altering the uptake pathway through reformulation by loading nanoparticles onto MBs.


Assuntos
Carbono , Microbolhas , Nanopartículas , Peixe-Zebra , Animais , Carbono/química , Camundongos , Nanopartículas/química , Células NIH 3T3 , Sistemas de Liberação de Medicamentos/métodos
5.
Adv Healthc Mater ; : e2400679, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38794813

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction. Current treatments, such as Methotrexate (MTX), though effective, often face limitations such as high plasma Cmax and lack of sustained release. This study explores a synergistic approach to RA therapy using folate-liposomal co-delivery of MTX and RELA siRNA (short interfering RNA), targeting RAW264.7 macrophage repolarization via nuclear factor kappa B (NF-κB) pathway inhibition. Extensive in vitro characterizations demonstrate the stability and biocompatibility of this therapy via folate-liposomes. In the collagen-induced arthritis (CIA) rat model, treatment leads to reduced synovial inflammation and improved mobility. The combined MTX and RELA siRNA approach indirectly inhibits inflammatory cytokines, rheumatoid factor (RF), and C-reactive protein (CRP). Targeted macrophage delivery shows marked therapeutic effects in RAW264.7 murine macrophages, potentially modulating M1 to M2 polarization. This research presents a promising avenue for innovative RA therapies by inhibiting the inflammatory cascade and preventing joint damage.

6.
J Biosci ; 492024.
Artigo em Inglês | MEDLINE | ID: mdl-38445557

RESUMO

Multiple endocytic processes operate in cells in tandem to uptake multiple cargoes involved in diverse cellular functions, including cell adhesion and migration. The best-studied clathrin-mediated endocytosis (CME) involves the formation of a well-defined cytoplasmic clathrin coat to facilitate cargo uptake. According to the glycolipid-lectin (GL-Lect) hypothesis, galectin-3 (Gal3) binds to glycosylated membrane receptors and glycosphingolipids (GSLs) to drive membrane bending and tubular membrane invaginations that undergo scission to form a morphologically distinct class of uptake structures, termed clathrin-independent carriers (CLICs). Which components from cytoskeletal machinery are involved in the scission of CLICs remains to be explored. In this study, we propose that dynein is recruited onto Gal3-induced tubular endocytic pits and provides the pulling force for friction-driven scission. The uptake of Gal3 and its cargoes (CD98/CD147) is significantly dependent on dynein activity, whereas only transferrin (CME marker) is slightly affected upon dynein inhibition. Our study reveals that Gal3 and Gal3-dependent (CD98 and CD147) clathrin-independent cargoes require dynein for the clathrin-independent endocytosis.


Assuntos
Endocitose , Galectina 3 , Galectina 3/genética , Endocitose/genética , Transporte Biológico , Clatrina , Dineínas
7.
Phys Chem Chem Phys ; 26(7): 6372-6385, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38315058

RESUMO

Self-assembly of ethylene oxide (EO)-propylene oxide (PO)-based star-shaped block copolymers (BCPs) in the presence of different kinds of additives is investigated in an aqueous solution environment. Commercially available four-armed BCPs, namely Tetronics® (normal: T904 with EO as the terminal end block; and reverse: T90R4 with PO as the terminal end block), each with 40%EO, are used. The effect of various additives such as electrolytes (NaCl and Na2SO4), nonelectrolyte polyols (glucose and sorbitol), and ionic surfactants (viz. anionic-sodium dodecyl sulfate (SDS), cationic-dodecyltrimethylammonium bromide (DTAB) and zwitterionic dodecyldimethylammonium propane sulfonate (C12PS)) on these BCPs is examined to observe their influence on micellization behaviour. The presence of salts and polyols displayed interesting phase behaviour, i.e., the cloud point (CP) was decreased, the water structure was affected and the micelles were dehydrated by expelling water molecules, and thus they were likely to promote micelle formation/growth. In contrast, ionic surfactants in small amounts interacted with the BCPs and showed an increase in CPs thereby forming mixed micelles with increasing charges and decreasing micellar sizes, finally transforming to small surfactant-rich mixed micelles. Molecular interactions such as electrostatic and hydrogen bonding involved within the examined entities are put forth employing a computational simulation approach using the Gaussian 09 window for calculation along with the GaussView 5.0.9 programming software using the (DFT)/B3LYP method and 3-21G basis set. The hydrodynamic diameter (Dh) of the micelles is examined using dynamic light scattering (DLS), while the various micellar parameters inferring the shape/geometry are obtained using small-angle neutron scattering (SANS) by the best fitting of the structure factors. It is observed that 10 w/v% T904 remains as spherical micelles with some micellar growth under physiological conditions (37 °C), while 10 w/v% T90R4 remains as unimers and forms spherical micelles in the presence of additives at 37 °C. Furthermore, the additive-induced micellar systems are tested as developing nanovehicles for anticancer (curcumin, Cur) drug solubilization using UV-vis spectroscopy, which shows a prominent increase in absorbance with enhanced solubilization capacity. Additionally, the cytotoxic effect of Cur loaded on the BCP micelles in HeLa cells is studied through confocal microscopy by capturing fluorescence images that depict HeLa cell growth inhibition under the influence of additive-induced micellar systems.

8.
Nanoscale Adv ; 6(2): 386-401, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38235105

RESUMO

DNA nanotechnology has significantly progressed in the last four decades, creating nucleic acid structures widely used in various biological applications. The structural flexibility, programmability, and multiform customization of DNA-based nanostructures make them ideal for creating structures of all sizes and shapes and multivalent drug delivery systems. Since then, DNA nanotechnology has advanced significantly, and numerous DNA nanostructures have been used in biology and other scientific disciplines. Despite the progress made in DNA nanotechnology, challenges still need to be addressed before DNA nanostructures can be widely used in biological interfaces. We can open the door for upcoming uses of DNA nanoparticles by tackling these issues and looking into new avenues. The historical development of various DNA nanomaterials has been thoroughly examined in this review, along with the underlying theoretical underpinnings, a summary of their applications in various fields, and an examination of the current roadblocks and potential future directions.

9.
ACS Omega ; 9(1): 1196-1205, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222585

RESUMO

Sonodynamic therapy (SDT) is a promising alternative to photodynamic therapy for achieving site-specific cytotoxic therapy. Porphyrin derivative molecules have been reported extensively in photodynamic therapy. We have previously shown that the glycosylation of porphyrin-based sonosensitizers can enhance their cellular uptake. However, the sonodynamic potential of these water-soluble glycosylated porphyrins has not been investigated. In this study, we characterized the sonodynamic response of two water-soluble glycosylated porphyrin derivatives. Ultrasound (US) exposure was performed (1 MHz frequency, intensities of 0.05-1.1 W/cm2) for 0-3 min in continuous mode. Reactive oxygen species (ROS) generation was quantified via ultraviolet-visible (UV-vis) spectrophotometry. MTT assay was used to quantify cytotoxicity caused by sonodynamic effects from these derivatives in the human mammary carcinoma (SUM-159) cell line in vitro. ROS generation from the porphyrin derivatives was demonstrated at a concentration of 15 µM. No significant cytotoxic effects were observed with the sonosensitizer alone or US exposure alone over the tested range of intensities and duration. The free base porphyrin derivative caused 60-70% cell death, whereas the zinc-porphyrin derivative with Zn metal conjugation caused nearly 50% cytotoxicity when exposed at 0.6 W/cm2 intensity for 3 min. These studies demonstrate the potential of anticancer SDT with soluble glycosylated porphyrins.

10.
Int J Biol Macromol ; 255: 128019, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952802

RESUMO

Worldwide, burn wounds are severe health issues prone to bacterial infections and challenging to treat with traditional wound dressings. Therefore, a highly desirable biological macromolecules-based wound dressing with good antioxidant, antibacterial, biocompatible, and a large surface area is required. Herein, aim to develop a biological macromolecules-based physically cross-linked gelatin/polyglyceryl stearate/graphene oxide (GPGO) hydrogel to treat burn wounds. Four sets of hydrogels were prepared by varying GO concentrations. FT-IR, FE-SEM, viscosity analysis, mechanical and thermal stability confirmed the successful preparation of hydrogels with desired properties. Further, ß-carotene (0.5 mg/mL) was encapsulated in hydrogels to enhance the antioxidant activity, and a cumulative release as well as kinetics at pH 6.4 and 7.4 was performed. With an increase in GO concentration, hydrogels showed sustained release of ß-carotene. Among all, GPGO-3 ß hydrogel showed the highest antioxidant potency (57.75 %), hemocompatible (<5 %), cytocompatible (viable with NIH 3T3 cells), cell migration, proliferation, and in vitro wound healing. Also, GPGO-3 ß hydrogel showed efficient antibacterial activity (%inhibition of 85.5 % and 80.2 % and zone of 11 mm and 9.8 mm against S. aureus and E. coli). These results demonstrated the ability of GPGO-3 ß hydrogel as a promising candidate for burn wound healing applications.


Assuntos
Queimaduras , Hidrogéis , Camundongos , Animais , Humanos , Hidrogéis/farmacologia , Hidrogéis/química , Antioxidantes/farmacologia , Gelatina/química , Estearatos , beta Caroteno , Staphylococcus aureus , Escherichia coli , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Queimaduras/tratamento farmacológico
11.
Biomaterials ; 303: 122390, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37984246

RESUMO

Rheumatoid arthritis (RA) is one of the most prevalent life-long autoimmune diseases with an unknown genesis. It primarily causes chronic inflammation, pain, and synovial joint-associated cartilage and bone degradation. Unfortunately, limited information is available regarding the etiology and pathogenesis of this chronic joint disorder. In the last few decades, an improved understanding of RA pathophysiology about key immune cells, antibodies, and cytokines has inspired the development of several anti-rheumatic drugs and biopharmaceuticals to act on RA-affected joints. However, life-long frequent systemic high doses of commercially available drugs are currently a limiting factor in the efficient management of RA. To address this issue, various single and double-barrier intra-articular drug delivery systems (IA-DDSs) such as nanocarriers, microparticles, hydrogels, and particles-hybrid hydrogel composite have been developed which can exclusively target the RA-affected joint cavity and release the precisely controlled therapeutic drug concentration for prolonged time whilst avoiding the systemic toxicity. This review provides a comprehensive overview of the pathogenesis of RA and discusses the rational design and development of biomaterials-based novel IA-DDs, ranging from conventional to advanced systems, for improved treatment of RA. Therefore, this review aims to unravel the pathophysiology of rheumatoid arthritis and explore cutting-edge IA-DD strategies exploiting biomaterials. It offers researchers a consolidated and up-to-date resource platform to analyze existing knowledge, identify research gaps, and contribute to the scientific literature.


Assuntos
Artrite Reumatoide , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/patologia , Articulações/metabolismo , Articulações/patologia , Sistemas de Liberação de Medicamentos , Inflamação/patologia , Materiais Biocompatíveis/uso terapêutico
12.
Chembiochem ; 24(21): e202300506, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37677117

RESUMO

Hypoxia, a decrease in cellular or tissue level oxygen content, is characteristic of most tumors and has been shown to drive cancer progression by altering multiple subcellular processes. We hypothesized that the cancer cells in a hypoxic environment might have slower proliferation rates and increased invasion and migration rates with altered endocytosis compared to the cancer cells in the periphery of the tumor mass that experience normoxic conditions. We induced cellular hypoxia by exposing cells to cobalt chloride, a chemical hypoxic mimicking agent. This study measured the effect of hypoxia on cell proliferation, migration, and invasion. Uptake of fluorescently labeled transferrin, galectin3, and dextran that undergo endocytosis through major endocytic pathways (Clathrin-mediated pathway (CME), Clathrin-independent pathway (CIE), Fluid phase endocytosis (FPE)) were analyzed during hypoxia. Also, the organelle changes associated with hypoxia were studied with organelle trackers. We found that the proliferation rate decreased, and the migration and invasion rate increased in cancer cells in hypoxic conditions compared to normoxic cancer cells. A short hypoxic exposure increased galectin3 uptake in hypoxic cancer cells, but a prolonged hypoxic exposure decreased clathrin-independent endocytic uptake of galectin 3. Subcellular organelles, such as mitochondria, increased to withstand the hypoxic stress, while other organelles, such as Endoplasmic reticulum (ER), were significantly decreased. These data suggest that hypoxia modulates cellular endocytic pathways with reduced proliferation and enhanced cell migration and invasion.


Assuntos
Hipóxia , Mitocôndrias , Humanos , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/patologia , Movimento Celular , Hipóxia Celular , Proliferação de Células , Mitocôndrias/metabolismo , Clatrina/metabolismo , Clatrina/farmacologia
13.
J Inorg Biochem ; 249: 112384, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37776828

RESUMO

Novel zinc porphyrins (trans-A2B2 and A3B type) are reported containing pharmacophoric groups derived from Sorafenib at the meso-positions. The pharmacophoric and bioisosteric modification of Sorafenib was done with 2-methyl-4-nitro-N-phenylaniline. The in-vitro photo-cytotoxicity studies of zinc porphyrins on HeLa cells revealed excellent PDT based autophagy inhibition of cancer cells, with IC50 values between 6.2 to 15.4 µM. The trans-A2B2 type zinc porphyrin with two bioisosteric groups gave better cytotoxicity than A3B type. Molecular docking studies revealed excellent binding with mTOR protein kinase of the designed porphyrins. The confocal studies indicated significant ER localization of trans-A2B2 type zinc porphyrin in HeLa cells along with ROS generation. trans-A2B2 type zinc porphyrin induced ER stress in cancer cells, thereby causing elevation of Ca+2 ions in cytoplasm, which led to cancer cell death via autophagy pathway. The studies suggested that trans-A2B2 and A3B type zinc porphyrins can be developed as theranostic agents for anti-cancer applications.


Assuntos
Fotoquimioterapia , Porfirinas , Humanos , Sorafenibe/farmacologia , Células HeLa , Simulação de Acoplamento Molecular , Medicina de Precisão , Porfirinas/química , Zinco/química , Fármacos Fotossensibilizantes/farmacologia
14.
Nanoscale Adv ; 5(17): 4337-4353, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37638168

RESUMO

Quantum dots (QDs), and carbon quantum dots (CDs) in particular, have received significant attention for their special characteristics. These particles, on the scale of several nanometers, are often produced using simple and green methods, with naturally occurring organic precursors. In addition to facile production methods, CDs present advantageous applications in the field of medicine, primarily for bioimaging, antibacterial and therapeutics. Also, CDs present great potential for surface modification through methods like doping or material mixing during synthesis. However, the bulk of current literature focuses on CDs emitting in the blue wavelengths which are not very suitable for biological applications. Red emitting CDs are therefore of additional interest due to their brightness, photostability, novelty and deeper tissue penetration. In this review article, red CDs, their methods of production, and their biological applications for translational research are explored in depth, with emphasis on the effects of surface modifications and doping.

15.
Nanoscale ; 15(31): 12785-12786, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37497680

RESUMO

An introduction to the Nanoscale, Nanoscale Advances and Physical Chemistry Chemical Physics (PCCP) themed collection on DNA and RNA nanotechnology, featuring a selection of excellent articles that highlight the potential of nucleic acids for various applications.


Assuntos
Ácidos Nucleicos , Ácidos Nucleicos/química , DNA/química , RNA/química , Nanotecnologia , Conformação de Ácido Nucleico
16.
Traffic ; 24(10): 434-452, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37392160

RESUMO

Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aß, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doenças Neurodegenerativas/metabolismo , Agregados Proteicos , Doença de Alzheimer/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo
17.
ACS Appl Bio Mater ; 6(7): 2886-2897, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37379246

RESUMO

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1 ± 0.08 nm, and a sustained kinetic release of curcumin was observed within 24 h. The nanoliposomes were further characterized using TEM, FTIR, and XRD, and the morphological changes in macrophage cells, RAW264.7, were observed in SEM, indicating a distinct M2-type phenotype after the treatment with liposomal curcumin. ROS may partially control macrophage polarization and be observed to decrease after treatment with liposomal curcumin. The nanoliposomes were able to successfully internalize in the macrophage cells, and an enhanced expression of ARG-1 and CD206 with a decrease in iNOS, CD80, and CD86 levels suggested the polarization of LPS-activated macrophages toward the M2 phenotype. Also, liposomal curcumin treatment dose-dependently inhibited TNF-α, IL-2, IFN-γ, and IL-17A at secretory levels and simultaneously increased the levels of cytokines like IL-4, IL-6, and IL-10.


Assuntos
Curcumina , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Macrófagos/metabolismo , Inflamação/tratamento farmacológico , Citocinas/metabolismo , Fenótipo
18.
Nanoscale Adv ; 5(9): 2558-2564, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37143798

RESUMO

Three-dimensional DNA nanocages have attracted significant attention for various biomedical applications including targeted bioimaging in vivo. Despite the numerous advantages, the use and in vivo exploration of DNA nanocages are limited as the cellular targeting and intracellular fate of these DNA nanocages within various model systems have not been explored well. Herein, using a zebrafish model system, we provide a detailed understanding of time-, tissue- and geometry-dependent DNA nanocage uptake in developing embryos and larvae. Of all the geometries tested, tetrahedrons showed significant internalization in 72 hours post-fertilized larvae upon exposure, without disturbing the expression of genes involved in embryo development. Our study provides a detailed understanding of the time and tissue-specific uptake of DNA nanocages in the zebrafish embryos and larvae. These findings will provide valuable insights into the internalization and biocompatible potential of DNA nanocages and will help to predict their candidature for biomedical applications.

19.
Chembiochem ; 24(10): e202300067, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-36862065

RESUMO

Functional DNA hydrogels with various motifs and functional groups require perfect sequence design to avoid cross-bonding interference with themselves or other structural sequences. This work reports an A-motif functional DNA hydrogel that does not require any sequence design. A-motif DNA is a noncanonical parallel DNA duplex structure containing homopolymeric deoxyadenosines (poly-dA) strands that undergo conformation changes from single strands at neutral pH to a parallel duplex DNA helix at acidic pH. Despite this and other advantages over other DNA motifs like no cross-bonding interference with other structural sequences, the A-motif has not been explored much. We successfully synthesized a DNA hydrogel by using an A-motif as a reversible handle to polymerize a DNA three-way junction. The A-motif hydrogel was initially characterized by electrophoretic mobility shift assay, and dynamic light scattering, which showed the formation of higher-order structures. Further, we used imaging techniques like atomic force microscopy and scanning electron microscope to validating its hydrogel like highly branched morphology. pH-induced conformation transformation from monomers to gel is quick and reversible, and was analysed for multiple acid-base cycles. The sol-to-gel transitions and gelation properties were further examined in rheological studies. The use of the A-motif hydrogel in the visual detection of pathogenic target nucleic acid sequence was demonstrated for the first time in a capillary assay. Moreover, pH-induced hydrogel formation was observed in situ as a layer over the mammalian cells. The proposed A-motif DNA scaffold has enormous potential in designing stimuli-responsive nanostructures that can be used for many biological applications.


Assuntos
Hidrogéis , Nanoestruturas , Animais , Hidrogéis/química , DNA/química , Motivos de Nucleotídeos , Nanoestruturas/química , Concentração de Íons de Hidrogênio , Mamíferos
20.
Chem Asian J ; 18(9): e202300044, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-36945757

RESUMO

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h. Interestingly, AAT also produce differential emission inside mouse normal cells as compared to its cancer cell lines since it possess anticancer activity. The experimental observations were also validated theoretically via computational modeling.


Assuntos
Espectrometria de Fluorescência , Animais , Camundongos , Espectrometria de Fluorescência/métodos , Sobrevivência Celular , Linhagem Celular , Solventes
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