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1.
Carbohydr Polym ; 337: 122159, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710574

RESUMO

Chitosan and chitosan derivatives can kill pathogenic microorganisms including bacteria and fungi. The antimicrobial activity is dependent on the degree of acetylation, substituent structure, and molecular weight. Over the past four decades, numerous studies have endeavored to elucidate the relationship between molecular weight and the activity against microorganisms. However, investigators have reported divergent and, at times, conflicting conclusions. Here a bilinear equation is proposed, delineating the relationship between antimicrobial activity, defined as log (1/MIC), and the molecular weight of chitosan and chitosan derivatives. Three constants AMin, AMax, and CMW govern the shape of the curve determined by the equation. The constant AMin denotes the minimal activity expected as the molecular weight tends towards zero while AMax represents the maximal activity observed for molecular weights exceeding CMW, the critical molecular weight required for max activity. This equation was applied to analyze data from seven studies conducted between 1984 and 2019, which reported MIC (Minimum Inhibitory Concentration) values against bacteria and fungi for various molecular weights of chitosan and its derivatives. All the 29 datasets exhibited a good fit (R2 ≥ 0.5) and half excellent (R2 ≥ 0.95) fit to the equation. The CMW generally ranged from 4 to 10 KD for datasets with an excellent fit to the equation.


Assuntos
Bactérias , Quitosana , Fungos , Testes de Sensibilidade Microbiana , Peso Molecular , Quitosana/química , Quitosana/farmacologia , Fungos/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Antibacterianos/farmacologia , Antibacterianos/química , Antifúngicos/farmacologia , Antifúngicos/química , Polímeros/química , Polímeros/farmacologia
2.
Colloids Surf B Biointerfaces ; 238: 113928, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38692175

RESUMO

In this research, four water-insoluble flavonoid compounds were utilized and reacted with arginine to prepare four carbonized polymer dots with good water-solubility in a hydrothermal reactor. Structural characterization demonstrated that the prepared carbonized polymer dots were classic core-shell structure. Effect of the prepared carbonized polymer dots on protein amyloid aggregation was further investigated using hen egg white lysozyme and human lysozyme as model protein in aqueous solution. All of the prepared carbonized polymer dots could retard the amyloid aggregation of hen egg white lysozyme and human lysozyme in a dose-depended manner. All measurements displayed that the inhibition ratio of luteolin-derived carbonized polymer dots (CPDs-1) was higher than that of the other three carbonized polymer dots under the same dosage. This result may be interpreted by the highest content of phenolic hydroxyl groups on the periphery. The inhibition ratio of CPDs-1 on hen egg white lysozyme and human lysozyme reached 88 % and 83 % at the concentration of 0.5 mg/mL, respectively. CPDs-1 also could disaggregate the formed mature amyloid fibrils into short aggregates.


Assuntos
Amiloide , Flavonoides , Muramidase , Polímeros , Agregados Proteicos , Muramidase/química , Muramidase/metabolismo , Humanos , Polímeros/química , Polímeros/farmacologia , Amiloide/química , Amiloide/antagonistas & inibidores , Flavonoides/química , Flavonoides/farmacologia , Agregados Proteicos/efeitos dos fármacos , Animais , Galinhas , Carbono/química
3.
Molecules ; 29(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731481

RESUMO

As the use of antibiotics increases, the increasing resistance of bacteria is the main reason for the reduced efficiency of antibacterial drugs, making the research of new antibacterial materials become new hot spot. In this article, two novel coordination polymers (CPs), namely, [Cd2(L)2(bibp)2]n (1) and [Ni(L)(bib)]n (2), where H2L = N,N'-bis(4-carbozvlbenzvl)-4-aminotoluene, bibp = 4,4'-bis(imidazol-1-yl)biphenyl, and bib = 1,3-bis(1-imidazoly)benzene, have been synthesized under solvothermal and hydrothermal condition. Structural clarification was performed through infrared spectrum and single-crystal X-ray diffraction analysis, while thermal analysis and XRD technology were used for the performance assessment of compounds 1 and 2. In addition, antibacterial performance experiments showed that compounds 1 and 2 have certain selectivity in their antibacterial properties and have good antibacterial properties against S. aureus. As the concentration of the compound increases, the inhibitory effect gradually strengthens, and when the concentration of the compound reaches 500 µg/mL and 400 µg/mL, the concentration of the S. aureus solution no longer increases and has been completely inhibited.


Assuntos
Antibacterianos , Testes de Sensibilidade Microbiana , Polímeros , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Polímeros/síntese química , Ligantes , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Estrutura Molecular , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/síntese química , Modelos Moleculares , Cristalografia por Raios X
4.
ACS Appl Bio Mater ; 7(5): 2862-2871, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38699864

RESUMO

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.


Assuntos
Antivirais , Heparitina Sulfato , Polímeros , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Heparitina Sulfato/química , Heparitina Sulfato/farmacologia , Animais , Humanos , Polímeros/química , Polímeros/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Culicidae/efeitos dos fármacos , Culicidae/virologia , Testes de Sensibilidade Microbiana , Teste de Materiais , Tamanho da Partícula , Linhagem Celular , Estrutura Molecular , Chlorocebus aethiops , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Zika virus/efeitos dos fármacos
5.
ACS Appl Bio Mater ; 7(5): 3283-3294, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38727030

RESUMO

Medical implants are constantly facing the risk of bacterial infections, especially infections caused by multidrug resistant bacteria. To mitigate this problem, gold nanoparticles with alkyl bromide moieties (Au NPs-Br) on the surfaces were prepared. Xenon light irradiation triggered the plasmon effect of Au NPs-Br to induce free radical graft polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA), leading to the formation of poly(DMAEMA) brush-grafted Au NPs (Au NPs-g-PDM). The Au NPs-g-PDM nanocomposites were conjugated with phytic acid (PA) via electrostatic interaction and van der Waals interaction. The as-formed aggregates were deposited on the titanium (Ti) substrates to form the PA/Au NPs-g-PDM (PAP) hybrid coatings through surface adherence of PA and the gravitational effect. Synergistic bactericidal effects of contact-killing caused by the cationic PDM brushes, and local heating generated by the Au NPs under near-infrared irradiation, conferred strong antibacterial effects on the PAP-deposited Ti (Ti-PAP) substrates. The synergistic bactericidal effects reduced the threshold temperature required for the photothermal sterilization, which in turn minimized the secondary damage to the implant site. The Ti-PAP substrates exhibited 97.34% and 99.97% antibacterial and antiadhesive efficacy, respectively, against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), compared to the control under in vitro antimicrobial assays. Furthermore, the as-constructed Ti-PAP surface exhibited a 99.42% reduction in the inoculated S. aureus under in vivo assays. In addition, the PAP coatings exhibited good biocompatibility in the hemolysis and cytotoxicity assays as well as in the subcutaneous implantation of rats.


Assuntos
Antibacterianos , Escherichia coli , Ouro , Teste de Materiais , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Ácido Fítico , Staphylococcus aureus , Ouro/química , Ouro/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Nanopartículas Metálicas/química , Ácido Fítico/química , Ácido Fítico/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Animais , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Cátions/química , Cátions/farmacologia , Polímeros/química , Polímeros/farmacologia , Titânio/química , Titânio/farmacologia
6.
ACS Appl Mater Interfaces ; 16(20): 25757-25772, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738757

RESUMO

The development of therapeutics with high antimicrobial activity and immunomodulatory effects is urgently needed for the treatment of infected wounds due to the increasing danger posed by recalcitrant-infected wounds. In this study, we developed light-controlled antibacterial, photothermal, and immunomodulatory biomimetic N/hPDA@M nanoparticles (NPs). This nanoplatform was developed by loading flavonoid naringenin onto hollow mesoporous polydopamine NPs in a π-π-stacked configuration and encasing them with macrophage membranes. First, our N/hPDA@M NPs efficiently neutralized inflammatory factors present within the wound microenvironment by the integration of macrophage membranes. Afterward, the N/hPDA@M NPs effectively dismantled bacterial biofilms through a combination of the photothermal properties of PDA and the quorum sensing inhibitory effects of naringenin. It is worth noting that N/hPDA@M NPs near-infrared-enhanced release of naringenin exhibited specificity toward the NF-κB-signaling pathway, effectively mitigating the inflammatory response. This innovative design not only conferred remarkable antibacterial properties upon the N/hPDA@M NPs but also endowed them with the capacity to modulate inflammatory responses, curbing excessive inflammation and steering macrophage polarization toward the M2 phenotype. As a result, this multifaceted approach significantly contributes to expediting the healing process of infected skin wounds.


Assuntos
Antibacterianos , Biofilmes , Indóis , NF-kappa B , Nanopartículas , Percepção de Quorum , Cicatrização , Biofilmes/efeitos dos fármacos , Nanopartículas/química , Camundongos , NF-kappa B/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Percepção de Quorum/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Flavanonas/química , Flavanonas/farmacologia , Células RAW 264.7 , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Polímeros/química , Polímeros/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Humanos
7.
Molecules ; 29(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792232

RESUMO

Poly(2-hydroxyethylmethacrylate-co-2-(dimethylamino)ethyl methacrylate), P(HEMA-co-DMAEMAx), copolymers were quaternized through the reaction of a part of (dimethylamino)ethyl moieties of DMAEMA units with 1-bromohexadecane. Antimicrobial coatings were further prepared through the cross-linking reaction between the remaining DMAEMA units of these copolymers and the epoxide ring of poly(N,N-dimethylacrylamide-co-glycidyl methacrylate), P(DMAm-co-GMAx), copolymers. The combination of P(HEMA-co-DMAEMAx)/P(DMAm-co-GMAx) copolymers not only enabled control over quaternization and cross-linking for coating stabilization but also allowed the optimization of the processing routes towards a more facile cost-effective methodology and the use of environmentally friendly solvents like ethanol. Careful consideration was given to achieve the right content of quaternized units, qDMAEMA, to ensure antimicrobial efficacy through an appropriate amphiphilic balance and sufficient free DMAEMA groups to react with GMA for coating stabilization. Optimal synthesis conditions were achieved by membranes consisting of cross-linked P(HEMA78-co-DMAEMA9-co-qDMAEMA13)/P(DMAm-co-GMA42) membranes. The obtained membranes were multifunctional as they were self-standing and antimicrobial, while they demonstrated a distinct fast response to changes in humidity levels, widening the opportunities for the construction of "smart" antimicrobial actuators, such as non-contact antimicrobial switches.


Assuntos
Anti-Infecciosos , Umidade , Metacrilatos , Metacrilatos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Reagentes de Ligações Cruzadas/química , Testes de Sensibilidade Microbiana , Polímeros/química , Polímeros/síntese química , Polímeros/farmacologia
8.
J Mater Chem B ; 12(21): 5085-5097, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38713059

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment associated with the accumulation of beta-amyloid protein (Aß). Aß activates glial cells in the brain, increasing the secretion of proinflammatory cytokines, which leads to neuroinflammation and neuronal death. Currently, there are no effective treatments that cure or stop its progression; therefore, AD is considered a global health priority. The main limitations are the low drug bioavailability and impermeability of the blood-brain barrier (BBB). Fortunately, nanomedicine has emerged as a promising field for the development of new nanosystems for the controlled and targeted delivery of drugs to the brain. Therefore, in this work, lipid-polymer hybrid nanoparticles (LPHNPs) conjugated with transferrin (Tf) to facilitate crossing the BBB and loaded with N-acetylcysteine (NAC) for its anti-inflammatory effect were synthesized, and their physicochemical characterization was carried out. Subsequently, an in vitro model involving human astrocytes derived from induced pluripotent stem cells (iPSC) from an AD-diagnosed patient was developed, which was brought to a reactive state by stimulation with lipopolysaccharides (LPSs). The cell culture was treated with either Tf-conjugated LPHNPs loaded with NAC (NAC-Tf-LPHNPs) at 0.25 mg mL-1, or free NAC at 5 mM. The results showed that NAC-Tf-LPHNPs favorably modulated the expression of proinflammatory genes such as interleukin-1ß (IL-1ß), amyloid precursor protein (APP) and glial fibrillary acidic protein (GFAP). In addition, they reduced the secretion of the proinflammatory cytokines interleukin 6 (IL-6), IL-1ß and interferon-gamma (INF-γ). Results for both cases were compared to the group of cells that did not receive any treatment. In contrast, free NAC only had this effect on the expression of IL-1ß and the secretion of the cytokines IL-6 and INF-γ. These results indicate the potential of NAC-Tf-LPHNPs for AD treatment.


Assuntos
Acetilcisteína , Doença de Alzheimer , Astrócitos , Células-Tronco Pluripotentes Induzidas , Nanopartículas , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Nanopartículas/química , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Acetilcisteína/química , Acetilcisteína/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Polímeros/química , Polímeros/farmacologia , Lipídeos/química , Biomarcadores/metabolismo , Tamanho da Partícula , Doenças Neuroinflamatórias/tratamento farmacológico
9.
Int J Biol Macromol ; 269(Pt 2): 132207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723823

RESUMO

To overcome the low efficacy of sonodynamic therapy (SDT) caused by hypoxia in the tumor microenvironment, we developed a multiple anti-tumor nanoplatform with synergistic SDT, photothermal therapy (PTT), and ferroptosis effects. PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption. FcCaO2 decomposed into H2O2 in the tumor microenvironment, triggering the Fenton effect to produce OH, and Cu2+ reduced the potential loss of OH by the depletion of GSH. Under ultrasonic (US) and laser irradiation, PFC exhibits exciting PTT and SDT effects from polydopamine (PDA) and PCN-224. Mn2+ not only promoted the reaction of H2O2 to produce O2 to effectively enhance SDT but also induced tumor cell apoptosis by Mn2+ combined with DHA. PFC induced ferroptosis via Fe interaction with DHA to produce ROS and reduce the expression of GPX4. The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.


Assuntos
Indóis , Estruturas Metalorgânicas , Terapia Fototérmica , Polímeros , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Humanos , Animais , Camundongos , Terapia Fototérmica/métodos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Linhagem Celular Tumoral , Nanopartículas/química , Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Terapia Combinada , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/química , Peróxido de Hidrogênio/farmacologia , Imiquimode/farmacologia , Metalocenos/química , Metalocenos/farmacologia
10.
Langmuir ; 40(21): 10957-10965, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38752656

RESUMO

Zwitterionic coatings provide a promising antifouling strategy against biofouling adhesion. Quaternary ammonium cationic polymers can effectively kill bacteria on the surface, owing to their positive charges. This strategy can avoid the release of toxic biocides, which is highly desirable for constructing coatings for biomedical devices. The present work aims to develop a facile method by covalently grafting zwitterionic and cationic copolymers containing aldehydes to the remaining amine groups of self-polymerized dopamine. Reversible addition-fragmentation chain transfer polymerization was used to copolymerize either zwitterionic 2-methacryloyloxyethyl phosphorylcholine monomer (MPC) or cationic 2-(methacryloyloxy)ethyl trimethylammonium monomer (META) with 4-formyl phenyl methacrylate monomer (FPMA), and the formed copolymers poly(MPC-st-FPMA) and poly(META-st-FPMA) are denoted as MPF and MTF, respectively. MPF and MTF copolymers were then covalently grafted onto the amino groups of polydopamine-coated surfaces. PDA/MPF/MTF-coated surfaces exhibited antibacterial and antifouling properties against S. aureus, E. coli, and bovine serum albumin protein. In addition, they showed excellent viability of normal human lung fibroblast cells MRC-5. We expect the facile surface modification strategy discussed here to be applicable to medical device manufacturing.


Assuntos
Antibacterianos , Polímeros , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Polímeros/química , Polímeros/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Incrustação Biológica/prevenção & controle , Escherichia coli/efeitos dos fármacos , Bivalves/química , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Fosforilcolina/farmacologia , Soroalbumina Bovina/química , Humanos , Metacrilatos/química , Metacrilatos/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Indóis
11.
Acta Biomater ; 180: 358-371, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604464

RESUMO

Glaucoma valves (GVs) play an essential role in treating glaucoma. However, fibrosis after implantation has limited their long-term success in clinical applications. In this study, we aimed to develop a comprehensive surface-engineering strategy to improve the biocompatibility of GVs by constructing a microenvironment-regulated and dual-hydrophilic antifouling coating on a GV material (silicone rubber, SR). The coating was based on a superhydrophilic polydopamine (SPD) coating with good short-range superhydrophilicity and antifouling abilities. In addition, SPD coatings contain many phenolic hydroxyl groups that can effectively resist oxidative stress and the inflammatory microenvironment. Furthermore, based on its in situ photocatalytic free-radical polymerization properties, the SPD coating polymerized poly 2-methylacryloxyethylphosphocholine, providing an additional long-range hydrophilic and antifouling effect. The in vitro test results showed that the microenvironment-regulated and dual-hydrophilic coatings had anti-protein contamination, anti-oxidation, anti-inflammation, and anti-fiber proliferation capabilities. The in vivo test results indicated that this coating substantially reduced the fiber encapsulation formation of the SR material by inhibiting inflammation and fibrosis. This design strategy for dual hydrophilic coatings with microenvironmental regulation can provide a valuable reference for the surface engineering design of novel medical implantable devices. STATEMENT OF SIGNIFICANCE: Superhydrophilic polydopamine (SPD) coatings were prepared on silicone rubber (SR) by a two-electron oxidation method. Introduction of pMPC to SPD surface using photocatalytic radical polymerization to obtain a dual-hydrophilic coating. The dual-hydrophilic coating effectively modulates the oxidative and inflammatory microenvironment. This coating significantly reduced protein contamination and adhesion of inflammatory cells and fibroblasts in vitro. The coating-modified SR inhibits inflammatory and fibrosis responses in vivo, promising to serve the glaucoma valves.


Assuntos
Materiais Revestidos Biocompatíveis , Implantes para Drenagem de Glaucoma , Interações Hidrofóbicas e Hidrofílicas , Polímeros , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Animais , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Propriedades de Superfície , Humanos , Glaucoma/patologia
12.
Acta Biomater ; 180: 183-196, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604465

RESUMO

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Magnésio , Nanocompostos , Stents , Animais , Coelhos , Magnésio/química , Magnésio/farmacologia , Nanocompostos/química , Corrosão , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Incrustação Biológica/prevenção & controle , Dioxanos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Polímeros/química , Polímeros/farmacologia , Ligas/química , Ligas/farmacologia
13.
Int J Biol Macromol ; 268(Pt 2): 131724, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38653427

RESUMO

The emergence of novel well-defined biological macromolecular architectures containing fluorine moieties displaying superior functionalities can satisfactorily address many biomedical challenges. In this research, ABA- and AB-type glucose-based biological macromolecules were synthesized using acryl-2,3,4,6-tetra-O-acetyl-D-glucopyranoside with pentafluorophenyl (FPM), pentafluorobenzyl (FBM), phenyl (PM) and benzyl (BM) methacrylate-based macro-RAFT agents following RAFT polymerization. The macro-RAFT agents and the corresponding copolymers were characterized by 19F, 1H, and 13C NMR and FTIR spectroscopic techniques to understand the chemical structure, molecular weight by size-exclusion chromatography, thermal analysis by TGA and DSC. Thermal stability (Td5%) of the FPM and FBM fluoro-based polymers was observed in the range of 219-267 °C, while the non-fluoro PM and BM polymers exhibited in the range of 216-264 °C. Among the macro-RAFT agents, PFPM (107 °C, ΔH: 0.613 J/g) and PPM (103 °C, ΔH: 0.455 J/g) showed higher Tm values, while among the block copolymers, PFBM-b-PG (123 °C, ΔH: 0.412 J/g) and PG-b-PFPM-b-PG (126 °C, ΔH: 0.525 J/g) exhibited higher Tm values. PFBMT and PPM macro-RAFT agents, PPM-b-PG and PG-b-PPM-b-PG copolymer spin-coated films showed the highest hydrophobicity (120°) among the synthesized polymers. The block copolymers exhibited self-assembled segregation by using relatively hydrophobic segments as the core and hydrophilic moieties as the corona. Synthesized biological macromolecules exhibit maximum antibacterial activity towards S. aureus than E. coli bacteria. Fluorophenyl (PFPM) and non-fluorobenzyl-based (PBMT) macro-RAFT agents exhibit low IC50 values, suggesting high cytotoxicity. All the triblock copolymers exhibit lesser cytotoxicity than the di-block polymers.


Assuntos
Glucose , Substâncias Macromoleculares , Glucose/química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Polímeros/química , Polímeros/síntese química , Polímeros/farmacologia , Humanos , Polimerização , Peso Molecular , Flúor/química , Técnicas de Química Sintética
14.
Nanotechnology ; 35(29)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38593752

RESUMO

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer.


Assuntos
Clorofilídeos , Indóis , Melaninas , Melanoma Experimental , Nanopartículas , Polímeros , Porfirinas , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Nanopartículas/química , Animais , Camundongos , Melanoma Experimental/patologia , Melanoma Experimental/terapia , Linhagem Celular Tumoral , Porfirinas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fototerapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Terapia Fototérmica
15.
ACS Appl Mater Interfaces ; 16(17): 21472-21485, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626344

RESUMO

Wound management is a major challenge worldwide, placing a huge financial burden on the government of every nation. Wound dressings that can protect wounds, accelerate healing, prevent infection, and avoid secondary damage continue to be a major focus of research in the health care and clinical communities. Herein, a novel zwitterionic polymer (LST) hydrogel incorporated with [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA), mussel-inspired N-[tris(hydroxymethyl)methyl] acrylamide (THMA), and lithium magnesium salt was prepared for functional wound dressings. The incorporation of the THMA monomer containing three hydroxyl groups gives the hydrogel suitable adhesion properties (∼6.0 KPa). This allows the LST zwitterionic hydrogels to bind well to the skin, which not only protects the wound and ensures its therapeutic efficacy but also allows for painless removal and reduced patient pain. Zwitterionic sulfobetaine units of SBMA provide antimicrobial and mechanical properties. The chemical structure and microscopic morphology of LST zwitterionic hydrogels were systematically studied, along with their swelling ratio, adhesion, and mechanical properties. The results showed that the LST zwitterionic hydrogels had a uniform and compact porous structure with the highest swelling and mechanical strain of 1607% and 1068.74%, respectively. The antibacterial rate of LST zwitterionic hydrogels was as high as 99.49%, and the hemostatic effect was about 1.5 times that of the commercial gelatin hemostatic sponges group. In further studies, a full-thickness mouse skin model was selected to evaluate the wound healing performance. Wounds covered by LST zwitterionic hydrogels had a complete epithelial reformation and new connective tissue, and its vascular regenerative capacity was increased to about 2.4 times that of the commercial group, and the wound could completely heal within 12-13 days. This study provides significant advances in the design and construction of multifunctional zwitterionic hydrogel adhesives and wound dressings.


Assuntos
Antibacterianos , Hidrogéis , Cicatrização , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Antibacterianos/química , Antibacterianos/farmacologia , Hemostáticos/química , Hemostáticos/farmacologia , Bandagens , Adesivos/química , Adesivos/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia
16.
ACS Appl Mater Interfaces ; 16(17): 22493-22503, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647220

RESUMO

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.


Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Indóis , Levodopa , Melaninas , Nanopartículas , Compostos de Amônio Quaternário , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Nanopartículas/química , Melaninas/química , Animais , Camundongos , Levodopa/química , Terapia Fototérmica , Humanos , Linhagem Celular Tumoral , Polímeros/química , Polímeros/síntese química , Polímeros/farmacologia
17.
ChemistryOpen ; 13(5): e202300223, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38647351

RESUMO

Silver/polymeric vesicle composite nanoparticles with good antibacterial properties were fabricated in this study. Silver nanoparticles (AgNPs) were prepared in situ on cross-linked vesicle membranes through the reduction of silver nitrate (AgNO3) using polyvinylpyrrolidone (PVP) via coordination bonding between the Ag+ ions and the nitrogen atoms on the vesicles. X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-vis), and transmission electron microscopy (TEM) analyses confirmed the formation of AgNPs on the vesicles. The antibacterial test demonstrated good antibacterial activity against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) for the produced AgNP-decorated vesicles. The minimum inhibitory concentration (MIC) values of the AgNP-decorated vesicles for E. coli and S. aureus were 8.4 and 9.6 µg/mL, respectively. Cell viability analysis on the A549 cells indicated that the toxicity was low when the AgNP concentrations did not exceed the MIC values, and the wound healing test confirmed the good antibacterial properties of the AgNP-decorated vesicles.


Assuntos
Antibacterianos , Escherichia coli , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Prata , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/toxicidade , Prata/química , Prata/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Sobrevivência Celular/efeitos dos fármacos , Células A549 , Polímeros/química , Polímeros/farmacologia
18.
ACS Appl Bio Mater ; 7(5): 2851-2861, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38587870

RESUMO

Periodontitis is a chronic oral inflammatory disease with the characteristic of excess oxidative stress in the inflammatory site, dramatically decreasing the quality of life. Studies show that nanozymes can be ideal candidates for ROS scavenging in periodontitis. Here, we design a multipath anti-inflammatory mesoporous polydopamine@cerium oxide nanobowl (mPDA@CeO2 NB) with multienzyme mimicking properties, which combines the advantages of both CeO2 NP and mPDA NB for synergistically eliminating reactive oxygen species (ROS), including hydroxyl radical (•OH), hydrogen peroxide (H2O2), and superoxide (O2•-). Besides, the erythrocyte-like structure of mNBs makes them a facility for cell uptake, and the mesopores can load both hydrophobic and hydrophilic drugs for combined anti-inflammatory therapy. In vitro and in vivo experiments prove that the combination of CeO2 and mPDA can synergistically achieve multiple complementary ROS eliminations and suppression of ROS-induced inflammation. Moreover, the ROS regulation plus anti-inflammatory drugs in one mPDA@CeO2 NB prevents the progression of periodontitis in a mouse model. Therefore, the design of mPDA@CeO2 NB with these excellent properties provides a therapeutic strategy for inflammatory diseases.


Assuntos
Cério , Indóis , Teste de Materiais , Tamanho da Partícula , Periodontite , Polímeros , Cério/química , Cério/farmacologia , Periodontite/tratamento farmacológico , Animais , Camundongos , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Porosidade , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
19.
ACS Appl Bio Mater ; 7(5): 3469-3482, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38651365

RESUMO

Bacterial invasion hinders the healing process of wound, leading to the formation of chronic infected wound; meanwhile, the misuse of antibiotics has resulted in the emergence of numerous drug-resistant bacteria. The application of conventional antimicrobial methods and wound treatment techniques is not appropriate for wound dressings. In this paper, quaternized poly(vinyl alcohol) (QPVA) and pomegranate-like copper uniformly doped polydopamine nanoparticles (PDA@Cu) were introduced into a gelatin-oxidized carboxymethyl cellulose system to form a multicomponent synergistic antibacterial hydrogel (GOQ3P3). Polydopamine improves the biocompatibility and prevents the detachment of Cu nanoparticles. It can achieve synergistic antibacterial effects through quaternary ammonium salt-inorganic nanoparticle photothermal treatment under 808 nm near-infrared (NIR) irradiation. It exhibits highly efficient and rapid bactericidal properties against Escherichia coli, Staphylococcus aureus, and MRSA (methicillin-resistant Staphylococcus aureus) with an antibacterial rate close to 100%. The gel scaffold composed of macromolecules gives the hydrogel excellent mechanical properties, adhesive capabilities, self-healing characteristics, biocompatibility, and pH degradation and promotes cell adhesion and migration. In a full-thickness wound healing model infected with MRSA, GOQ3P3 controls inflammatory responses, accelerates collagen deposition, promotes angiogenesis, and enhances wound closure in the wound healing cascade reaction. This study provides a feasible strategy for constructing dressings targeting chronic infection wounds caused by drug-resistant bacteria.


Assuntos
Antibacterianos , Materiais Biocompatíveis , Carboximetilcelulose Sódica , Escherichia coli , Gelatina , Hidrogéis , Teste de Materiais , Testes de Sensibilidade Microbiana , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Gelatina/química , Cicatrização/efeitos dos fármacos , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Escherichia coli/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Tamanho da Partícula , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Cobre/química , Cobre/farmacologia , Humanos
20.
ACS Appl Bio Mater ; 7(5): 2966-2981, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38652577

RESUMO

This study presents a facile fabrication of 58S bioactive glass (BG)-polymer composite coatings on a 316L stainless steel (SS) substrate using the electrophoretic deposition technique. The suspension characteristics and deposition kinetics of BG, along with three different polymers, namely ethylcellulose (EC), poly(acrylic acid) (PAA), and polyvinylpyrrolidone (PVP), have been utilized to fabricate the coatings. Among all coatings, 58S BG and EC polymers are selected as the final composite coating (EC6) owing to their homogeneity and good adhesion. EC6 coating exhibits a thickness of ∼18 µm and an average roughness of ∼2.5 µm. Herein, EC6 demonstrates better hydroxyapatite formation compared to PAA and PVP coatings in simulated body fluid-based mineralization studies for a period of 28 days. Corrosion studies of EC6 in phosphate-buffered saline further confirm the higher corrosion resistance properties after 14 days. In vitro cytocompatibility studies using human placental mesenchymal stem cells demonstrate an increase in cellular viability, attachment, and higher proliferation compared to the bare SS substrate. EC6 coatings promote osteogenic differentiation, which is confirmed via the upregulation of the OPN and OCN genes. Moreover, the EC6 sample exhibits improved antibacterial properties against Escherichia coli and Staphylococcus aureus compared to the uncoated ones. The findings of this work emphasize the potential of electrophoretically fabricated BG-EC composite coatings on SS substrates for orthopedic applications.


Assuntos
Materiais Revestidos Biocompatíveis , Vidro , Teste de Materiais , Polímeros , Aço Inoxidável , Aço Inoxidável/química , Humanos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Vidro/química , Polímeros/química , Polímeros/farmacologia , Corrosão , Tamanho da Partícula , Propriedades de Superfície , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Eletroforese , Sobrevivência Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Testes de Sensibilidade Microbiana , Proliferação de Células/efeitos dos fármacos
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