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1.
J Vis Exp ; (212)2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39431782

RESUMEN

Antibiotics are currently the most used antibacterial treatment for killing bacteria. However, bacteria develop resistance when continually overexposed to antibiotics. Developing antimicrobial agents that can replace existing antibiotics is essential because antibiotic-resistant bacteria have resistance mechanisms for all current antibiotics and can promote nosocomial infections. To address this challenge, in this study, we propose graphene oxide/copper (GO/Cu) nanocomposites as antibacterial materials that can replace the existing antibiotics. GO/Cu nanocomposites are characterized by transmission electron microscopy and scanning electron microscopy. They show that copper (Cu) nanoparticles are well-grown on the graphene oxide sheets. Additionally, a microdilution broth method is used to confirm the efficacy of the antimicrobial substance against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa), which are frequently implicated in nosocomial infections. Specifically, 99.8% of MRSA and 84.7% of P. aeruginosa are eliminated by 500 µg/mL of GO/Cu nanocomposites. Metal nanocomposites can eradicate antibiotic-resistant bacteria by releasing ions, forming reactive oxygen species, and physically damaging the bacteria. This study demonstrates the potential of antibacterial GO/Cu nanocomposites in eradicating antibiotic-resistant bacteria.


Asunto(s)
Antibacterianos , Cobre , Grafito , Staphylococcus aureus Resistente a Meticilina , Nanocompuestos , Pseudomonas aeruginosa , Grafito/química , Grafito/farmacología , Cobre/química , Cobre/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Nanocompuestos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos
2.
Nano Converg ; 11(1): 40, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39406944

RESUMEN

Microplastics, particularly those in the micrometer scale, have been shown to enter the human body through ingestion, inhalation, and dermal contact. Recent research indicates that microplastics can potentially impact the central nervous system (CNS) by crossing the blood-brain barrier (BBB). However, the exact mechanisms of their transport, uptake, and subsequent toxicity at BBB remain unclear. In this study, we evaluated the size-dependent uptake and cytotoxicity of polystyrene microparticles using an engineered BBB model. Our findings demonstrate that 0.2 µm polystyrene microparticles exhibit significantly higher uptake and transendothelial transport compared to 1.0 µm polystyrene microparticles, leading to increased permeability and cellular damage. After 24 h of exposure, permeability increased by 15.6-fold for the 0.2 µm particles and 2-fold for the 1.0 µm particles compared to the control. After 72 h of exposure, permeability further increased by 27.3-fold for the 0.2 µm particles and a 4.5-fold for the 1.0 µm particles compared to the control. Notably, microplastics administration following TNF-α treatment resulted in enhanced absorption and greater BBB damage compared to non-stimulated conditions. Additionally, the size-dependent toxicity observed differently between 2D cultured cells and 3D BBB models, highlighting the importance of testing models in evaluating environmental toxicity.

3.
J Vis Exp ; (211)2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39400132

RESUMEN

Nosocomial bacterial infections have become increasingly challenging due to their inherent resistance to antibiotics. The emergence of multidrug-resistant bacterial strains in hospitals has been attributed to the extensive and varied use of antibiotics, further exacerbating the problem of antibiotic resistance. Metal nanomaterials have been widely studied as an alternative solution for eradicating antibiotic-resistant bacterial cells. Metallic nanoparticles attack bacterial cells through various mechanisms, such as the release of antibacterial ions, generation of reactive oxygen species, or physical disruption, against which bacteria cannot develop resistance. Among the actively researched antimicrobial metal nanoparticles, zinc oxide nanoparticles, which are FDA-approved, are known for their biocompatibility and antibacterial properties. In this study, we focused on successfully developing a precipitation method for synthesizing zinc oxide nanoparticles, analyzing the properties of these nanoparticles, and conducting antimicrobial tests. Zinc oxide nanoparticles were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), ultraviolet/visible spectroscopy, and X-ray diffraction (XRD). Antibacterial tests were conducted using the broth microdilution test with the multidrug-resistant strains of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. This study demonstrated the potential of zinc oxide nanoparticles in inhibiting the proliferation of antibiotic-resistant bacteria.


Asunto(s)
Antibacterianos , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Pseudomonas aeruginosa , Óxido de Zinc , Óxido de Zinc/química , Óxido de Zinc/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Nanopartículas del Metal/química , Pruebas de Sensibilidad Microbiana
4.
ACS Chem Neurosci ; 15(17): 3220-3227, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39155540

RESUMEN

The unique architecture of the brain and the blood-brain barrier imposes challenges for the measurement of parenchyma-derived biomarkers that prevent sufficient understanding of transient neuropathogenic processes. One solution to this challenge is direct sampling of brain interstitial fluid via implanted microperfusion probes. Seeking to understand spatial limitations to microperfusion in the brain, we employed computational fluid dynamics modeling and empirical recovery of fluorescently labeled dextrans in an animal model. We found that dextrans were successfully recovered via microperfusion over a 6 h sampling period, especially at probes implanted 2 mm from the dextran infusion point relative to probes implanted 5 mm from the injection site. Experimental recovery was consistently around 1% of simulated, suggesting that this parameter can be used to set practical limits on the maximal tissue concentration of proteins measured in microperfusates and on the spatial domain sampled by our multimodal microperfusion probe.


Asunto(s)
Encéfalo , Dextranos , Animales , Encéfalo/metabolismo , Masculino , Tejido Parenquimatoso/metabolismo , Líquido Extracelular/metabolismo , Líquido Extracelular/química , Perfusión/métodos , Barrera Hematoencefálica/metabolismo , Hidrodinámica , Ratas
5.
IUCrdata ; 9(Pt 6): x240539, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38974849

RESUMEN

The title cobalt(II) complex, [Co(C2H3N)3(C9H21N3)](C24H20B)2 or [(tacn)Co(NCMe)3][BPh4]2, has been characterized by single-crystal X-ray diffraction. It incorporates the well-known macrocyclic tacn (1,4,7-trimethyl-1,4,7-tri-aza-cyclo-nona-ne) ligand, which is coordinated facially to the metal center. The complex crystallizes in space group P21/c with Z = 4. The divalent cobalt ion exhibits a six-coordinate octa-hedral geometry by one tacn and three aceto-nitrile ligands. Two non-coordinating tetra-phenyl-borate (BPh4 -) anions are also present.

6.
J Hazard Mater ; 476: 135193, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39029192

RESUMEN

While the hazardous effects of microplastics (MPs) are increasingly reported, it remains uncertain if MPs induce inner ear dysfunction. Nonetheless, prevalence of inner ear dysfunction was observed across all age groups. In this study, we investigated whether MP polyethylene affect inner ear function in a murine model. To detect hearing loss and balance defect after polyethylene (PE) exposure, we evaluated hearing threshold levels, assessed cerebral glucose metabolism, conducted transcriptome analysis, and performed behavioral studies. C57BL/6 J mice (5-week-old) were grouped into control (n = 10) and PE-fed groups (n = 10). Mice were orally administered 100 ppm/100 µL (equivalent to 10 µg) of PE every day for 4 months. We identified the accumulation of PE in the cochlea and vestibular region. The fragmented PE in inner ear was 3.00 ± 0.38 µm in size; the administered PE concentration was 1.14 ± 1.06 mg/g. Fourier transform infrared spectrometry confirmed that the properties of the MP were identical with those of PE fed to the mice. Transcriptomic analysis showed up-regulation of PER1, NR4A3 and CEBPB at the PE exposed inner ear tissue and it was confirmed using qRT-PCR, western blotting, and immunofluorescence staining. We observed abnormalities in balance related behavior assessment in the PE group. Exposure to PE increased the hearing thresholds and decreased glucose metabolism in the bilateral lateral entorhinal cortex, right primary auditory cortex, and right secondary auditory cortex. We can conclude that PE exposure induced inner ear dysfunction such as hearing loss and balance disorder.


Asunto(s)
Oído Interno , Ratones Endogámicos C57BL , Microplásticos , Polietileno , Animales , Polietileno/toxicidad , Oído Interno/efectos de los fármacos , Oído Interno/metabolismo , Microplásticos/toxicidad , Masculino , Ratones , Glucosa/metabolismo , Pérdida Auditiva/inducido químicamente , Equilibrio Postural/efectos de los fármacos , Modelos Animales de Enfermedad
7.
Angew Chem Int Ed Engl ; 63(39): e202408457, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-38853142

RESUMEN

Nitrogen oxides (NOx) are major environmental pollutants and to neutralize this long-term environmental threat, new catalytic methods are needed. Although there are biological denitrification processes involving four different enzymatic reactions to convert nitrate (NO3 -) into dinitrogen (N2), it is unfortunately difficult to apply in industry due to the complexity of the processes. In particular, nitrate is difficult to functionalize because of its chemical stability. Thus, there is no organometallic catalysis to convert nitrate into useful chemicals. Herein, we present a nickel pincer complex that is effective as a bifunctional catalyst to stepwise deoxygenate NO3 - by carbonylation and further through C-N coupling. By using this nickel catalysis, nitrate salts can be selectively transformed into various oximes (>20 substrates) with excellent conversion (>90 %). Here, we demonstrate for the first time that the highly inert nitrate ion can be functionalized to produce useful chemicals by a new organonickel catalysis. Our results show that the NOx conversion and utilization (NCU) technology is a successful pathway for environmental restoration coupled with value-added chemical generation.

8.
Inorg Chem ; 63(25): 11660-11666, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38861724

RESUMEN

Hybrid nanoparticles (NPs) have attracted considerable attention because of their ability to provide diverse properties by integrating the inherent properties of multiple components; however, synthetic strategies to control their morphology remain unexplored. In this study, a new method was used to control the morphology and optical properties of Au-Ni heterostructure (ANH) NPs. Unique morphological changes were observed by varying the Au/Ni precursor ratio from 2:1 to 1:4, exhibiting a shape transformation from dumbbell-like to quasi-spherical owing to the Ni NP size expansion, whereas the Au NP maintained their size. Moreover, increasing the Ni ratio induced plasmonic band broadening and wavelength redshift, resulting in color changes from red to navy and black. In terms of the structure, the atomic orientation of the crystallite showed that even a large lattice mismatch can result in heterojunctions at the NPs. In addition, the reaction aliquots uncovered heterogeneous nucleation and growth of ANH NPs in the colloidal system, demonstrating Ni reduction on the preformed Au NP owing to the reduction in potential gap. This study provides new insights into controlling the morphology of hybrid NPs using colloidal synthesis and the design of optimized materials for various applications.

9.
Acta Biomater ; 180: 140-153, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38604467

RESUMEN

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.


Asunto(s)
Neoplasias de la Mama , Galio , Hidrogeles , Hidrogeles/química , Galio/química , Galio/farmacología , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Animales , Línea Celular Tumoral , Inyecciones , Fototerapia , Ratones Desnudos , Ratones , Terapia Fototérmica , Ratones Endogámicos BALB C
10.
Microorganisms ; 12(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38543574

RESUMEN

Blastocystis sp. is the most common intestinal protozoan affecting human health worldwide. Several studies have reported the prevalence of Blastocystis sp. in various regions of the Republic of Korea. However, limited data are available on the prevalence and subtype (ST) distribution of this parasite among regions. Therefore, we investigated the prevalence and ST distributions of this parasite in the Republic of Korea. For this purpose, 894 stool specimens were collected from patients with diarrhea and tested for the presence of Blastocystis sp. using PCR analysis. The isolates were subsequently subtyped. The overall prevalence was 11.6%. Of the 104 isolates, ST3 was the most prevalent, followed by ST1. Additionally, a single case of the rare subtype ST8 was identified, representing the first reported case in the Republic of Korea. The results suggested that the predominance of ST3 observed in this study reflects human-to-human transmission with low genetic diversity within the ST, while ST1 transmission is likely correlated with animals. In the future, to better understand Blastocystis sp. transmission dynamics, human, animal, and environmental factors should be studied from a "One Health" perspective.

11.
Biomater Sci ; 12(8): 2007-2018, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38456516

RESUMEN

Background: drugs for Alzheimer's disease (AD) fail to exhibit efficacy in clinical trials for a number of reasons, a major one being blood-brain barrier (BBB) permeability. Meanwhile, the increasing incidence of this disease emphasizes the need for effective therapeutics. Herein, we discuss novel nanoplatform technologies developed for the effective delivery of AD drugs by traversing the BBB. Main text: the interfacial and surface chemistry of nanomaterials is utilized in several industries, including pharmaceutical, and has drawn considerable attention in the field of nanotechnology. Various reports have suggested the potential of nanotechnology for AD treatment, describing unique drug carriers that improve drug stability and solubility while maintaining therapeutic dosages. These nanotechnologies are harnessed for the transport of drugs across the BBB, with or without surface modifications. We also discuss the transfer of drugs via the nose-to-brain pathway, as intranasal delivery enables direct drug distribution in the brain. In addition, nanomaterial modifications that prolong drug delivery and improve safety following intranasal administration are addressed. Conclusion: although several studies have yielded promising results, limited efforts have been undertaken to translate research findings into clinical contexts. Nevertheless, nanomaterials hold considerable potential for the development of novel effective therapeutic solutions against AD.


Asunto(s)
Enfermedad de Alzheimer , Nanopartículas , Humanos , Barrera Hematoencefálica/metabolismo , Administración Intranasal , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/metabolismo , Nanotecnología
12.
Biosensors (Basel) ; 14(3)2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38534247

RESUMEN

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides' termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Plásticos/análisis , Plásticos/química , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Péptidos
13.
ACS Appl Bio Mater ; 7(4): 2175-2185, 2024 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-38478917

RESUMEN

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.


Asunto(s)
Curcumina , Liposomas , Neoplasias Pulmonares , Nanopartículas , Humanos , Curcumina/farmacología , Curcumina/química , Manosa , Lípidos , Neoplasias Pulmonares/tratamiento farmacológico
14.
Chemosphere ; 346: 140567, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38303386

RESUMEN

In the contemporary context, executing light-oxidant- and reductant-driven reactions in solution-phase processes remains challenging mainly due to the lack of general tools for understanding the reactive potential of nano-functional catalysts. In this study, dual-active nanometals (Au and Cu doped with Au) capped within soy lecithin (SL), were developed and characterized, combining flexibility with the catalytic advantages and stability of liquid-phase catalysts. The as-synthesized SL-Au (LG) and SL-Au-Cu (LGC) catalysts were efficiently degraded rhodamine B (RB, 100%) in the presence of H2O2 under light irradiation (350 W lamp) at wide pH range (3-7) within 4.5 h and p-nitrophenol (p-NP, >90% degradation at pH 7) in the presence of NaBH4 under normal stirring with slower kinetics (∼72 h). RB degradation followed a pseudo-second-order kinetic model with a higher r2, and p-NP degradation followed first-order kinetics. The active sites embedded within the structural order of SL arrangement displayed elevated catalytic activity, which was further enhanced by the movement of intermediate/excited states and charged elements within the metal suspended in the phospholipid (LG and LGC). The self-regulating tunability of the physicochemical characteristics of these catalysts provides a convenient and generalizable platform for the transformation of modern dual-active (redox) catalysts into dynamic homogeneous equivalents.


Asunto(s)
Peróxido de Hidrógeno , Peróxidos , Peróxido de Hidrógeno/química , Borohidruros , Fosfolípidos , Oxidación-Reducción , Suspensiones
15.
ACS Appl Bio Mater ; 7(2): 1146-1157, 2024 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-38282578

RESUMEN

Rotator cuff tears are currently treated with drugs (steroids and nonsteroidal anti-inflammatory drugs) and surgery. However, the damaged rotator cuff requires a considerable amount of time to regenerate, and the regenerated tissue cannot restore the same level of function as that before the damage. Although growth factors can accelerate regeneration, they are difficult to be used alone because of the risk of degradation and the difficulties in ensuring their sustained release. Thus, hydrogels such as gelatin are used, together with growth factors. Gelatin is a biocompatible and biodegradable hydrogel derived from collagen; therefore, it closely resembles the components of native tissues and can retain water and release drugs continuously, while also showing easily tunable mechanical properties by simple modifications. Moreover, gelatin is a natural biopolymer that possesses the ability to form hydrogels of varying compositions, thereby facilitating effective cross-linking. Therefore, gelatin can be considered to be suitable for rotator-to-tendon healing. In this study, we designed photo-cross-linkable gelatin hydrogels to enhance spacing and adhesive effects for rotator cuff repair. We mixed a ruthenium complex (Ru(II)bpy32+) and sodium persulfate into gelatin-based hydrogels and exposed them to blue light to induce gelation. Basic fibroblast growth factor and bone morphogenetic protein-12 were encapsulated in the gelatin hydrogel for localized and sustained release into the wound, thereby enhancing the cell proliferation. The effects of these dual growth factor-loaded hydrogels on cell cytotoxicity and tendon regeneration in rotator cuff tear models were evaluated using mechanical and histological assessments. The findings confirmed that the gelatin hydrogel was biocompatible and that treatment with the dual growth factor-loaded hydrogels in in vivo rotator cuff tear models promoted regeneration and functional restoration in comparison with the findings in the nontreated group. Therefore, growth factor-loaded gelatin-based hydrogels may be suitable for the treatment of rotator cuff tears.


Asunto(s)
Lesiones del Manguito de los Rotadores , Manguito de los Rotadores , Humanos , Manguito de los Rotadores/patología , Manguito de los Rotadores/cirugía , Lesiones del Manguito de los Rotadores/tratamiento farmacológico , Lesiones del Manguito de los Rotadores/patología , Lesiones del Manguito de los Rotadores/cirugía , Hidrogeles/farmacología , Gelatina/farmacología , Preparaciones de Acción Retardada , Tendones , Péptidos y Proteínas de Señalización Intercelular/farmacología
16.
Adv Healthc Mater ; 13(5): e2302313, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38124514

RESUMEN

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.


Asunto(s)
Vesículas Extracelulares , Nanopartículas Multifuncionales , Neoplasias Pancreáticas , Humanos , Lectinas/metabolismo , Polisacáridos , Neoplasias Pancreáticas/diagnóstico , Vesículas Extracelulares/metabolismo
17.
ACS Appl Bio Mater ; 2023 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-37586084

RESUMEN

Antiretroviral drugs are limited in their ability to target latent retroviral reservoirs in CD4+ T cells, highlighting the need for a T cell-targeted drug delivery system that activates the transcription of inactivated viral DNA in infected cells. Histone deacetylase inhibitors (HDACi) disrupt chromatin-mediated silencing of the viral genome and are explored in HIV latency reversal. But single drug formulations of HDACi are insufficient to elicit therapeutic efficacy, warranting combination therapy. Furthermore, protein kinase C activators (PKC) have shown latency reversal activity in HIV by activating the NF-κB signaling pathway. Combining HDACi (SAHA) with PKC (PMA) activators enhances HIV reservoir activation by promoting chromatin decondensation and subsequent transcriptional activation. In this study, we developed a mixed nanomicelle (PD-CR4) drug delivery system for simultaneous targeting of HIV-infected CD4+ T cells with two drugs, suberoylanilide hydroxamic acid (SAHA) and phorbol 12-myristate 13-acetate (PMA). SAHA is a HDACi that promotes chromatin decondensation, while PMA is a PKC agonist that enhances transcriptional activation. The physicochemical properties of the formulated PD-CR4 nanoparticles were characterized by NMR, CMC, DLS, and TEM analyses. Further, we investigated in vitro safety profiles, targeting efficacy, and transcriptional activation of inactivated HIV reservoir cells. Our results suggest that we successfully prepared a targeted PD system with dual drug loading. We have compared latency reversal efficacy of a single drug nanoformulation and combination drug nanoformulation. Final PD-SP-CR4 successfully activated infected CD4+ T cell reservoirs and showed enhanced antigen release from HIV reservoir T cells, compared with the single drug treatment group as expected. To summarize, our data shows PD-SP-CR4 has potential T cell targeting efficiency and efficiently activated dormant CD4+ T cells. Our data indicate that a dual drug-loaded particle has better therapeutic efficacy than a single loaded particle as expected. Hence, PD-CR4 can be further explored for HIV therapeutic drug delivery studies.

18.
Nanoscale Adv ; 5(17): 4536-4545, 2023 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-37638172

RESUMEN

Non-tuberculous mycobacterial infections are representative difficult-to-cure lung diseases with high incidence. Conventional treatments have several limitations such as negative side effects and increased drug resistance due to long-term administration. To overcome these limitations, there is a growing need for more stable drug delivery systems. Among the various drug delivery platforms developed thus far, solid lipid nanoparticles can be effectively loaded with hydrophobic substances and their physicochemical properties can be easily manipulated through surface modification, which makes them highly suitable drug delivery materials. Recent studies have reported the successful development of nanoparticles capable of selectively delivering drugs by targeting lectin-like receptors overexpressed on the surface of immune cells. Among these lectin-like receptors, the mannose receptor is a promising target because it is expressed on the surface of macrophages and is involved in immune activity. This study sought to synthesize rifampicin-loaded mannose surface-modified solid lipid nanoparticles (Man-RIF SLNs). The Man-RIF SLN synthesis process was first optimized, after which the characteristics of the synthesized particles were analyzed using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The surface modification with mannose was confirmed through FT-IR analysis. More importantly, the synthesized Man-RIF SLNs exhibited antibacterial and anti-biofilm properties against Mycobacterium intracellulare, a causative agent of non-tuberculous lung disease. Therefore, this study demonstrated that mannose receptor-targeted rifampicin delivery through solid lipid nanoparticles can be effectively applied to the treatment of non-tuberculous lung disease. Moreover, Man-RIF SLNs could also be used for the targeted delivery of drugs to several types of carcinoma cells or immune cells, as well as to treat lung diseases.

19.
Nanomaterials (Basel) ; 13(13)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37446533

RESUMEN

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

20.
Sci Rep ; 13(1): 11947, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37488203

RESUMEN

Infectious pathogens can be transmitted through textiles. Therefore, additional efforts are needed to develop functional fabrics containing antimicrobial substances to prevent the growth of antibiotic-resistant bacteria and their biofilms. Here, we developed a cotton fabric coated with reduced graphene oxide (rGO) and copper nanoparticles (Cu NPs), which possessed hydrophobic, antimicrobial, and anti-biofilm properties. Once the graphene oxide was dip-coated on a cellulose cotton fabric, Cu NPs were synthesized using a chemical reduction method to fabricate an rGO/Cu fabric, which was analyzed through FE-SEM, EDS, and ICP-MS. The results of our colony-forming unit assays indicated that the rGO/Cu fabric possessed high antibacterial and anti-biofilm properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Corynebacterium xerosis, and Micrococcus luteus. Particularly, the fabric could inhibit the growth of E. coli, C. xerosis, and M. luteus with a 99% efficiency. Furthermore, our findings confirmed that the same concentrations of rGO/Cu had no cytotoxic effects against CCD-986Sk and Human Dermal Fibroblast (HDF), human skin cells, and NIH/3T3, a mouse skin cell. The developed rGO/Cu fabric thus exhibited promising applicability as a cotton material that can maintain hygienic conditions by preventing the propagation of various bacteria and sufficiently suppressing biofilm formation while also being harmless to the human body.


Asunto(s)
Grafito , Humanos , Animales , Ratones , Cobre , Escherichia coli , Antibacterianos , Textiles
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