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1.
Dalton Trans ; 53(34): 14315-14324, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39135450

RESUMO

The design of multifunctional nanocarriers with enhanced photothermal efficiency is of great significance for the photothermal therapy of cancer. In this study, hollow CuS@gold nanorods/polydopamine (HCuS@AuNRs/PDA) nanohybrids with synergistically enhanced photothermal efficiency were prepared by electrostatic self-assembly method. The high photothermal conversion efficiency of HCuS@AuNRs (55.88%) is attributed to the interfacial electron transfer between CuS and AuNRs, as well as the increase in free charge carrier concentration. The excellent adhesion performance and strong negative charge of PDA ensure a high doxorubicin hydrochloride (DOX) loading efficiency of 96.08% for HCuS@AuNRs/PDA. In addition, HCuS@AuNRs/PDA reveals outstanding NIR/pH dual-responsive drug release properties owing to the weakened interaction between PDA and DOX in acidic media and the distinct NIR responsiveness of HCuS@AuNRs. In vitro cell viability results confirm that HCuS@AuNRs/PDA could efficiently kill tumor cells under the dual effect of acidic media and NIR laser. This study presents a novel nanocarrier with synergistically enhanced NIR photothermal responsiveness and high drug loading capacity, which provides a versatile platform in intelligent drug release and photothermal therapy.


Assuntos
Sobrevivência Celular , Cobre , Doxorrubicina , Ouro , Indóis , Polímeros , Doxorrubicina/farmacologia , Doxorrubicina/química , Ouro/química , Humanos , Sobrevivência Celular/efeitos dos fármacos , Polímeros/química , Indóis/química , Indóis/farmacologia , Cobre/química , Cobre/farmacologia , Nanotubos/química , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Terapia Fototérmica , Fototerapia , Linhagem Celular Tumoral
2.
Smart Med ; 3(2): e20240004, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39188699

RESUMO

The development of non-antibiotic pharmaceuticals with biocompatible and efficient antibacterial properties is of great significance for the treatment of bacterial keratitis. In this study, we have developed antibacterial iron-doped nanozymes (Fe3+-doped nanozymes, FNEs) with distinguished capacity to fight against bacterial infections. The iron-doped nanozymes are composed of Fe3+ doped zeolitic imidazolate framework-8 (Fe/ZIF-8) and polyethylene imide (PEI), which were functionally coated on the surface of Fe/ZIF-8 and imparted the FNEs with improved water dispersibility and biocompatibility. FNEs possess a significant spontaneous peroxidase-mimic activity without the need for external stimulation, thus elevating cellular reactive oxygen species level by catalyzing local H2O2 at the infection site and resulting in bacteria damaged to death. FNEs eliminated 100% of Staphylococcus aureus within 6 h, and significantly relieved inflammation and bacterial infection levels in mice bacterial keratitis, exhibiting higher bioavailability and a superior therapeutic effect compared to conventional antibiotic eye drops. In addition, the FNEs would not generate drug resistance, suggesting that FNEs have great potential in overcoming infectious diseases caused by antimicrobial resistant bacteria.

3.
Heliyon ; 10(11): e32506, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38961930

RESUMO

Purpose: To report the clinical, tomographic, histopathological and genetic findings of a patient with brittle cornea syndrome and a novel mutation in the ZNF469 gene likely implicated in the development of this disorder. Methods: A 64-year-old man presented with a two-year history of worsening vision in both eyes. The patient and his son were examined by imaging and genetic analysis. Results: The patient exhibited persistent ocular irritation, decreased vision, corneal epithelial defects and corneal stromal opacity. Confocal microscopy revealed that the anterior corneal stroma had a large amount of highly reflective and striated tissue. However, his son had no symptoms. Genetic analysis identified a heterozygous c.1781C > T:p.P594L variation in the ZNF469 gene. Conclusions: We reported a novel mutation in the ZNF469 gene (c.1781C > T:p.P594L) in a patient with brittle cornea syndrome from China, which enriched the spectrum of ZNF469 variants implicated in brittle cornea syndrome.

4.
J Hazard Mater ; 476: 134956, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38917630

RESUMO

Covalent organic frameworks (COFs) are a type of novel organic catalysts which show great potential in the treatment of environmental contaminations. Herein, we synthesized three isoreticular halogen-functionalized (F, Cl and Br) porphyrin COFs for visible-light (420 nm ≤ λ ≤ 780 nm) photocatalytic reduction of Cr(VI) to Cr(III). Halogen substituents with tunable electronegativity can regulate the band structure and modulate the charge carrier kinetics of COFs. In the absence of any sacrificial reagent, the isoreticular COFs exhibited good photocatalytic reduction activity of Cr(VI). Particularly, the TAPP-2F showed nearly 100 % conversion efficiency and the highest reaction rate constants (k) on account of the strong electronegativity of F substituent. Experimental results and theoretical calculations showed that the conduction band (CB) potentials of COFs became more negative and charge carrier separation increased with the enhancement of electronegativity (Br < Cl < F), which could provide sufficient driving force for the photoreduction of Cr(VI) to Cr(III). The halogen substituents strategy for regulating the electronic structure of COFs can provide opportunities for designing efficient photocatalysts for environmental remediation. Meanwhile, the mechanistic insights reported in this study help to understand the photocatalytic degradation pathways of heavy metals.

5.
Eur J Pharm Biopharm ; 201: 114352, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38851459

RESUMO

Subconjunctival fibrosis is critical to the outcomes of several ophthalmic conditions or procedures, such as glaucoma filtering surgery. This study aimed to investigate the anti-fibrotic effect of celastrol on subconjunctival fibrosis and to further reveal the underlying mechanisms. We used celastrol-loaded nanomicelles hydrogel hybrid as a sustained-release drug. A rabbit model of subconjunctival fibrosis following silicone implantation was used for in vivo study, and TGF-ß1-induced human pterygium fibroblast (HPF) activation as an in vitro model. The effects of celastrol on inhibiting TGF-ß1-induced migration and proliferation of HPFs were evaluated by scratch wound assay and CCK-8, respectively. Immunofluorescence and western blotting were used to examine the effect of celastrol on the expression of α-SMA, collagen I, fibronectin, and the targets of the Hippo signaling pathway. We found that in vivo celastrol treatment reduced the expression of YAP and TAZ in subconjunctival tissue. Moreover, celastrol alleviated collagen deposition and subconjunctival fibrosis at 8 weeks. No obvious tissue toxicity was observed in the rabbit models. Mechanistically, celastrol significantly inhibited TGF-ß1-induced proliferation and migration of HPFs. Pretreatment of HPFs with celastrol also suppressed the TGF-ß1-induced protein expression of α-SMA, collagen I, fibronectin, TGF-ßRII, phosphorylated Smad2/3, YAP, TAZ, and TEAD1. In conclusion, celastrol effectively prevented subconjunctival fibrosis through inhibiting TGF-ß1/Smad2/3-YAP/TAZ pathway. Celastrol could serve as a promising therapy for subconjunctival fibrosis.


Assuntos
Fibrose , Glaucoma , Triterpenos Pentacíclicos , Animais , Coelhos , Fibrose/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Glaucoma/cirurgia , Glaucoma/tratamento farmacológico , Humanos , Silicones , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Proliferação de Células/efeitos dos fármacos , Masculino , Hidrogéis , Triterpenos/farmacologia , Triterpenos/administração & dosagem , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/metabolismo , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Túnica Conjuntiva/metabolismo , Próteses e Implantes/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Preparações de Ação Retardada , Doenças da Túnica Conjuntiva/prevenção & controle
6.
Nanotechnology ; 35(33)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829163

RESUMO

Dry eye disease (DED) is a major global eye disease leading to severe eye discomfort and even vision impairment. The incidence of DED has been gradually increasing with the high frequency of use of electronic devices. It has been demonstrated that celastrol (Cel) has excellent therapeutic efficacy in ocular disorders. However, the poor water solubility and short half-life of Cel limit its further therapeutic applications. In this work, a reactive oxygen species (ROS) sensitive polymeric micelle was fabricated for Cel delivery. The micelles improve the solubility of Cel, and the resulting Cel loaded micelles exhibit an enhanced intervention effect for DED. Thein vitroresults demonstrated that Cel-nanomedicine had a marked ROS responsive release behavior. The results ofin vitroandin vivoexperiments demonstrated that Cel has excellent biological activities to alleviate inflammation in DED by inhibiting TLR4 signaling activation and reducing pro-inflammatory cytokine expression. Therefore, the Cel nanomedicine can effectively eliminate ocular inflammation, promote corneal epithelial repair, and restore the number of goblet cells and tear secretion, providing a new option for the treatment of DED.


Assuntos
Síndromes do Olho Seco , Micelas , Nanomedicina , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio , Triterpenos , Síndromes do Olho Seco/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Nanomedicina/métodos , Triterpenos/farmacologia , Triterpenos/química , Inflamação/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Humanos , Lágrimas/metabolismo , Lágrimas/efeitos dos fármacos
7.
J Nanobiotechnology ; 22(1): 229, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720321

RESUMO

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.


Assuntos
Síndromes do Olho Seco , Soluções Oftálmicas , Espécies Reativas de Oxigênio , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Síndromes do Olho Seco/tratamento farmacológico , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Álcool de Polivinil/química , Humanos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Boratos/química , Nanopartículas/química , Masculino
8.
Drug Dev Res ; 85(4): e22198, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38764200

RESUMO

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Glicólise , Neoplasias Hepáticas , Pantoprazol , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/metabolismo , Camundongos , Pantoprazol/farmacologia , Masculino , Proliferação de Células/efeitos dos fármacos , Humanos , Camundongos Endogâmicos C57BL , Carcinogênese/efeitos dos fármacos , Dietilnitrosamina/toxicidade , Citocinas/metabolismo , Linhagem Celular Tumoral , Dieta Hiperlipídica/efeitos adversos
9.
J Control Release ; 369: 604-616, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582337

RESUMO

Corneal stromal fibrosis is a common cause of visual impairment resulting from corneal injury, inflammation and surgery. Therefore, there is an unmet need for inhibiting corneal stromal fibrosis. However, bioavailability of topical eye drops is very low due to the tear and corneal barriers. In situ delivery offers a unique alternative to improve efficacy and minimize systemic toxicity. Herein, a drug delivery platform based on thermoresponsive injectable hydrogel/nano-micelles composite with in situ drug-controlled release and long-acting features is developed to prevent corneal scarring and reduce corneal stromal fibrosis in lamellar keratoplasty. The in-situ gelation hydrogels enabled direct delivery of celastrol to the corneal stroma. In vivo evaluation with a rabbit anterior lamellar keratoplasty model showed that hydrogel/micelles platform could effectively inhibit corneal stromal fibrosis. This strategy achieves controlled and prolonged release of celastrol in the corneal stroma of rabbit. Following a single corneal interlamellar injection, celastrol effectively alleviated fibrosis via mTORC1 signal promoting autophagy and inhibiting TGF-ß1/Smad2/3 signaling pathway. Overall, this strategy demonstrates promise for the clinical application of celastrol in preventing corneal scarring and reducing corneal stromal fibrosis post-lamellar keratoplasty, highlighting the potential benefits of targeted drug delivery systems in ocular therapeutics.


Assuntos
Transplante de Córnea , Hidrogéis , Triterpenos Pentacíclicos , Animais , Coelhos , Triterpenos Pentacíclicos/administração & dosagem , Hidrogéis/administração & dosagem , Transplante de Córnea/métodos , Cicatriz/prevenção & controle , Cicatriz/tratamento farmacológico , Preparações de Ação Retardada , Fibrose , Sistemas de Liberação de Medicamentos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Triterpenos/administração & dosagem , Liberação Controlada de Fármacos , Substância Própria/efeitos dos fármacos , Humanos
10.
J Am Chem Soc ; 146(17): 12000-12010, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38639553

RESUMO

The development of redox-conductive metal-organic frameworks (MOFs) and the fundamental understanding of charge propagation through these materials are central to their applications in energy storage, electronics, and catalysis. To answer some unresolved questions about diffusional electron hopping transport and redox conductivity, mixed-linker MOFs were constructed from two statistically distributed redox-active linkers, pyromellitic diimide bis-pyrazolate (PMDI) and naphthalene diimide bis-pyrazolate (NDI), and grown as crystalline thin films on conductive fluorine-doped tin oxide (FTO). Owing to the distinct redox properties of the linkers, four well-separated and reversible redox events are resolved by cyclic voltammetry, and the mixed-linker MOFs can exist in five discrete redox states. Each state is characterized by a unique spectroscopic signature, and the interconversions between the states can be followed spectroscopically under operando conditions. With the help of pulsed step-potential spectrochronoamperometry, two modes of electron propagation through the mixed-linker MOF are identified: diffusional electron hopping transport between linkers of the same type and a second channel that arises from thermodynamically driven electron transfers between linkers of different types. Corresponding to the four redox events of the mixed-linker MOFs, four distinct bell-shaped redox conductivity profiles are observed at a steady state. The magnitude of the maximum redox conductivity is evidenced to be dependent on the distance between redox hopping sites, analogous to the situation for apparent electron diffusion coefficients, Deapp, that are obtained in transient experiments. The design of mixed-linker redox-conductive MOFs and detailed studies of their charge transport properties present new opportunities for future applications of MOFs, in particular, within electrocatalysis.

11.
Nano Lett ; 24(13): 4044-4053, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517749

RESUMO

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.


Assuntos
Úlcera da Córnea , Infecções Oculares Fúngicas , Ceratite , Animais , Camundongos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Córnea/microbiologia
12.
Nanomicro Lett ; 16(1): 120, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372846

RESUMO

Dry eye disease (DED) is a major ocular pathology worldwide, causing serious ocular discomfort and even visual impairment. The incidence of DED is gradually increasing with the high-frequency use of electronic products. Although inflammation is core cause of the DED vicious cycle, reactive oxygen species (ROS) play a pivotal role in the vicious cycle by regulating inflammation from upstream. Therefore, current therapies merely targeting inflammation show the failure of DED treatment. Here, a novel dual-atom nanozymes (DAN)-based eye drops are developed. The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer. The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS, inhibiting NLRP3 inflammasome activation, decreasing proinflammatory cytokines expression, and suppressing cell apoptosis. Consequently, the DAN effectively alleviate ocular inflammation, promote corneal epithelial repair, recover goblet cell density and tear secretion, thus breaking the DED vicious cycle. Our findings open an avenue to make the DAN as an intervention form to DED and ROS-mediated inflammatory diseases.

13.
Ann Med ; 56(1): 2313680, 2024 12.
Artigo em Inglês | MEDLINE | ID: mdl-38335557

RESUMO

PURPOSE: To evaluate the role of M2 macrophages in subconjunctival fibrosis after silicone implantation (SI) and investigate the underlying mechanisms. MATERIALS AND METHODS: A model of subconjunctival fibrosis was established by SI surgery in rabbit eyes. M2 distribution and collagen deposition were evaluated by histopathology. The effects of M2 cells on the migration (using wound-scratch assay) and activation (by immunofluorescence and western blotting) of human Tenon's fibroblasts (HTFs) were investigated. RESULTS: There were more M2 macrophages (CD68+/CD206+ cells) occurring in tissue samples around silicone implant at 2 weeks postoperatively. Dense collagen deposition was observed at 8 weeks after SI. In vitro experiment showed M2 expressed high level of CD206 and transforming growth factor-ß1 (TGF-ß1). The M2-conditioned medium promoted HTFs migration and the synthesis of collagen I and fibronectin. Meanwhile, M2-conditioned medium increased the protein levels of TGF-ß1, TGF-ßR II, p-Smad2/3, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ). Verteporfin, a YAP inhibitor, suppressedTGF-ß1/Smad2/3-YAP/TAZ pathway and attenuated M2-induced extracellular matrix deposition by HTFs. CONCLUSIONS: TGF-ß1/Smad2/3-YAP/TAZ signalling may be involved in M2-induced fibrotic activities in HTFs. M2 plays a key role in promoting subconjunctival fibrosis and can serve as an attractive target for anti-fibrotic therapeutics.


Assuntos
Macrófagos , Fator de Crescimento Transformador beta1 , Animais , Humanos , Coelhos , Colágeno , Meios de Cultivo Condicionados , Fibrose , Macrófagos/metabolismo , Silicones , Fator de Crescimento Transformador beta1/metabolismo , Proteínas de Sinalização YAP/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo
14.
Eur J Pharm Sci ; 192: 106629, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37918544

RESUMO

Fungal keratitis (FK) is a serious infectious corneal disease that leads to blindness. Butenafine (BTF) is an allylamine drug with high antifungal activity, but its poor water solubility and low bioavailability limit its clinical application in ophthalmology. To increase its aqueous solubility and corneal permeability, butenafine was encapsulated in d-ɑ-tocopheryl polyethylene glycol succinate (TPGS) polymeric nanomicelles to improve the bioavailability of the drug for the treatment of FK. Butenafine was successfully fabricated into nanomicelles with a high EE of 96.34 ± 1.65 % and DL of 6.71 ± 0.099 %. The BTF-NM showed an average particle size of 13.12 ± 0.24 nm, a zeta potential of -0.56 ± 0.44 mV and a narrow PDI of 0.12 ± 0.02 with a nearly spherical shape. The characterization results of FTIR, XRD and DSC indicated that BTF was encapsulated in the TPGS nanomicelles. The BTF-NM formulation also showed high storage stability, and the in vitro drug release study showed typical biphasic-release characteristics. In addition, the BTF-NM formulation displayed good cellular tolerance and excellent ocular tolerance in rabbits. Significantly elevated in vitro antifungal activity was also observed in the BTF-NM formulation, and remarkable improvements regarding in vivo corneal permeation were observed compared with the BTF suspension formulation. Finally, the in vivo antifungal activity studies indicated that the BTF-NM formulation had a good therapeutic effect on FK and had similar efficacy to that of commercial natamycin suspension eye drops. These results suggest that the BTF-NM ophthalmic formulation could be a promising ocular drug delivery system for the treatment of FK.


Assuntos
Antifúngicos , Ceratite , Animais , Coelhos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Córnea , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Portadores de Fármacos/farmacologia , Tamanho da Partícula
15.
Molecules ; 28(24)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38138556

RESUMO

This study investigated the antivirulence capacity and mechanism of apple-skin-derived phloretin against Serratia marcescens NJ01, a vegetable spoilage bacterium. At 0.5 to 2 mg/mL doses, phloretin considerably inhibited the secretion of acyl homoserine lactones (AHLs), indicating that phloretin disrupted quorum sensing (QS) in S. marcescens NJ01. The dysfunction of QS resulted in reduced biofilms and the decreased production of protease, prodigiosin, extracellular polysaccharides (EPSs), and swimming and swarming motilities. Dysfunctional QS also weakened the activity of antioxidant enzymes and improved oxidative injury. The improved oxidative injury changed the composition of the membrane, improved membrane permeability, and eventually increased the susceptibility of biofilm cells to amikacin, netilmicin, and imipenem. The disrupted QS and enhanced oxidative stress also caused disorders of amino acid metabolism, energy metabolism, and nucleic acid metabolism, and ultimately attenuated the ability of S. marcescens NJ01 to induce spoilage. Our results indicated that phloretin can act as a potent drug to defend against spoilage by S. marcescens.


Assuntos
Percepção de Quorum , Serratia marcescens , Serratia marcescens/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Biofilmes , Prodigiosina/farmacologia
16.
Int J Biol Macromol ; 253(Pt 5): 127150, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37778587

RESUMO

The near-infrared (NIR)/pH dual-responsive nanoplatform shows great potential in remote photothermal therapy for tumor on account of the near-infrared window in biological tissue and the mild acidic environment in tumor cells. CuS nanoplatform has become a rising star in the field of photothermal agents due to its excellent NIR responsiveness and photostability. In this work, hollow CuS nanoparticles with high photothermal conversion efficiency (42.42 %) were synthesized through a novel surfactant micelle-assisted method. Then, CuS@hydroxyapatite (HAP)/hyaluronic acid (HA) nanoclusters with controllable drug release property were prepared by capping HAP and HA on the surface of CuS via electrostatic self-assembly approach. The hollow structure of CuS and the large specific surface area of HAP ensure an outstanding doxorubicin hydrochloride (DOX) loading efficiency of 99.2 % in CuS@HAP/HA nanoclusters. The introduction of HA effectively retards the initial burst release of DOX and ensures the excellent biocompatibility of nanoclusters. More importantly, CuS@HAP/HA displays distinct NIR/pH dual-responsive drug release properties owing to the excellent NIR responsiveness of hollow CuS and the gradual dissolution of HAP under acidic conditions. This work provides an environmentally benign method to prepare CuS-based nanoclusters with excellent NIR/pH responsive drug delivery properties, which has great potential in remote photothermal therapy.


Assuntos
Ácido Hialurônico , Nanopartículas , Ácido Hialurônico/química , Durapatita , Sistemas de Liberação de Medicamentos , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanopartículas/química , Concentração de Íons de Hidrogênio , Liberação Controlada de Fármacos
17.
ACS Infect Dis ; 9(10): 2005-2015, 2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37788827

RESUMO

The eyelid-related disease of blepharitis remains a tricky ocular disorder and affects patient compliance. However, there is no available and effective treatment, making it extremely challenging. Herein, an antibacterial system based on antibiotic delivery was developed and applied in a blepharitis model induced by bacteria. The antibacterial tests against Staphylococcus aureus both in vitro and in vivo demonstrated that the system shows a favorable bactericidal effect. Then, histological evaluation indicated that the system shows both antibacterial and anti-inflammatory effects. This facile design provided an effective ocular infection management, which displays a promising prospect while addressing other complex ocular disorders.


Assuntos
Antibacterianos , Blefarite , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Blefarite/tratamento farmacológico , Blefarite/microbiologia , Bactérias , Staphylococcus aureus , Resultado do Tratamento
18.
ACS Nano ; 17(21): 21595-21603, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37851935

RESUMO

The power of isoreticular chemistry has been widely exploited to engineer metal-organic frameworks (MOFs) with fascinating molecular sieving and storage properties but is underexplored for designing MOFs with tunable optoelectronic properties. Herein, three dipyrazole-terminated XDIs (X = PM (pyromellitic), N (naphthalene), or P (perylene); DI = diimide) with different lengths and electronic properties are prepared and employed as linkers for the construction of an isoreticular series of Zn-XDI MOFs with distinct electrochromism. The MOFs are grown on fluorine-doped tin oxide (FTO) as high-quality crystalline thin films and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Due to the constituting electronically isolated XDI linkers, each member of the isoreticular thin film series exhibits two reversible one-electron redox events, each at a distinct electrochemical potential. The orientation of the MOFs as thin films as well as their isoreticular nature results in identical cation-coupled electron hopping transport rates in all three materials, as demonstrated by comparable apparent electron diffusion coefficients, Deapp. Upon electrochemical reduction to either the [XDI]•- or [XDI]2- state, each MOF undergoes characteristic changes in its optical properties as a function of linker length and redox state of the linker. Operando spectroelectrochemistry measurements reveal that Zn-PDI@FTO (PDI = perylene diimide) thin films exhibit a record high coloration efficiency of 941 cm2 C-1 at 746 nm, which is attributed to the maximized Faradaic transformations at each electronically isolated PDI unit. The electrochromic response of the thin film is retained to more than 99% over 100 reduction-oxidation cycles, demonstrating the applicability of the presented materials.

19.
Angew Chem Int Ed Engl ; 62(45): e202312276, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37728510

RESUMO

Developing low-cost and efficient photocatalysts to convert CO2 into valuable fuels is desirable to realize a carbon-neutral society. In this work, we report that polymer dots (Pdots) of poly[(9,9'-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-thiadiazole)] (PFBT), without adding any extra co-catalyst, can photocatalyze reduction of CO2 into CO in aqueous solution, rendering a CO production rate of 57 µmol g-1 h-1 with a detectable selectivity of up to 100 %. After 5 cycles of CO2 re-purging experiments, no distinct decline in CO amount and reaction rate was observed, indicating the promising photocatalytic stability of PFBT Pdots in the photocatalytic CO2 reduction reaction. A mechanistic study reveals that photoexcited PFBT Pdots are reduced by sacrificial donor first, then the reduced PFBT Pdots can bind CO2 and reduce it into CO via their intrinsic active sites. This work highlights the application of organic Pdots for CO2 reduction in aqueous solution, which therefore provides a strategy to develop highly efficient and environmentally friendly nanoparticulate photocatalysts for CO2 reduction.

20.
Heliyon ; 9(8): e18853, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37600383

RESUMO

Purpose: To report a novel technique to facilitate amniotic membrane transplantation (AMT) for acute stage Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Design: Laboratory investigation and retrospective, single-center case series. Methods: The polylactic acid (PLA) amniotic fornical ring (AFR) have been successfully manufactured by three-dimensional (3D) printing technology for AMT. This study retrospectively analyzed the medical records of 5 SJS/TEN patients at the acute stage between 2019 and 2023. Patients were surgically treated with AFR or sutured amniotic membrane transplant (SAMT). Epidemiology, best-corrected visual acuity (BCVA), acute ocular severity score, operative duration, epithelial healing time, amniotic dissolution and follow-up time were evaluated. Results: Of all five patients, three patients (6 eyes) received AFR/AMT (Group A), and 2 patients (4 eyes) received SAMT (Group B). There were no significant differences between two groups in the mean preoperative days and vision changes. The mean operation duration was 11.7 ± 3.8 mins in group A. Compared with the SAMT (48.8 ± 5.3 mins), the operation duration was reduced by 76.02%. The mean times for epithelial healing were 32.5 ± 29.2 days in group A and 12.0 ± 0.0 days in group B. In addition, there were no significant side effects of 3D-printed sterile AFR on the eyes. Conclusions: 3D-printed PLA scaffolds could be used as an AFR device for acute SJS/TEN. In addition, personalized 3D-printed AFR is superior to conventional SAMT in operation duration.

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