RESUMO
Purpose: We aimed to prepare a ß-cyclodextrin (ß-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-ß-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the ß-CD polymer and REB (REB@CDQA) combination in treating dry eye. Methods: The ß-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model). Results: The solubility of the CDQA powder was higher than that of the ß-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the ß-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation. Conclusion: The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.
Assuntos
Acetilcisteína , Alanina , Modelos Animais de Doenças , Síndromes do Olho Seco , Quinolonas , Animais , Coelhos , Síndromes do Olho Seco/tratamento farmacológico , Quinolonas/farmacologia , Quinolonas/química , Quinolonas/administração & dosagem , Acetilcisteína/farmacologia , Acetilcisteína/química , Acetilcisteína/administração & dosagem , Humanos , Alanina/análogos & derivados , Alanina/química , Alanina/farmacologia , Alanina/administração & dosagem , Polímeros/química , Polímeros/farmacologia , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Polimerização , Ratos , Solubilidade , Cátions/química , beta-Ciclodextrinas/química , Córnea/efeitos dos fármacos , Córnea/metabolismo , Masculino , Estrutura MolecularRESUMO
Bleeding and bacterial infection are common problems associated with wound treatment, while effective blood clotting and vessel regeneration promotion are the primary considerations to design the wound dressing materials. This research presents a chitosan-based hydrogel with grafted quaternary ammonium and polyphosphate (QCSP hydrogel) as the antibacterial hemostatic dressing to achieve burn wound treatment. The tissue adhesion of the hydrogel sealed the blood flow and the polyphosphate grafted to the chitosan promoted the activation of coagulation factor V to enhance the hemostasis. At the same time, the grafted quaternary ammonium enhanced the antibacterial ability of the biodegradable hydrogel wound dressing. In addition, the polydopamine as a photothermal agent was composited into the hydrogel to enhance the antibacterial and reactive oxygen scavenging performance. The in vivo hemostasis experiment proved the polyphosphate enhanced the coagulation property. Moreover, this photothermal property of the composite hydrogel enhanced the burn wound repairing rate combined with the NIR stimulus. As a result, this hydrogel could have potential application in clinic as dressing material for hemostasis and infection prone would repairing.
Assuntos
Antibacterianos , Queimaduras , Quitosana , Hemostasia , Hidrogéis , Indóis , Polímeros , Cicatrização , Quitosana/química , Quitosana/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Queimaduras/tratamento farmacológico , Queimaduras/terapia , Polímeros/química , Polímeros/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Animais , Indóis/química , Indóis/farmacologia , Cicatrização/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Camundongos , Hemostáticos/química , Hemostáticos/farmacologia , Bandagens , Masculino , Ratos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Ratos Sprague-Dawley , Testes de Sensibilidade Microbiana , Terapia Fototérmica/métodosRESUMO
Introduction. As growing numbers of patients are at higher risk of infection, novel topical broad-spectrum antimicrobials are urgently required for wound infection management. Robust pre-clinical studies should support the development of such novel antimicrobials.Gap statement. To date, evidence of robust investigation of the cytotoxicity and antimicrobial spectrum of activity of antimicrobial peptides (AMP)s is lacking in published literature. Using a more clinical lens, we address this gap in experimental approach, building on our experience with poly-l-lysine (PLL)-based AMP polymers.Aim. To evaluate the in vitro bactericidal activity and cytotoxicity of a PLL-based 16-armed star AMP polymer, designated 16-PLL10, as a novel candidate antimicrobial.Methods. Antimicrobial susceptibilities of clinical isolates and reference strains of ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogens, to 16-PLL10 were investigated. Human erythrocyte haemolysis and keratinocyte viability assays were used to assess toxicity. Modifications were made to 16-PLL10 and re-evaluated for improvement.Results. Minimum bactericidal concentration of 16-PLL10 ranged from 1.25 µM to ≥25 µM. At 2.5 µM, 16-PLL10 was broadly bactericidal against ESKAPE strains/wound isolates. Log-reduction in colony forming units (c.f.u.) per millilitre after 1 h, ranged from 0.3 (E. cloacae) to 5.6 (K. pneumoniae). At bactericidal concentrations, 16-PLL10 was toxic to human keratinocyte and erythrocytes. Conjugates of 16-PLL10, Trifluoroacetylated (TFA)-16-PLL10, and Poly-ethylene glycol (PEG)ylated 16-PLL10, synthesised to address toxicity, only moderately reduced cytotoxicity and haemolysis.Conclusions. Due to poor selectivity indices, further development of 16-PLL10 is unlikely warranted. However, considering the unmet need for novel topical antimicrobials, the ease of AMP polymer synthesises/modification is attractive. To support more rational development, prioritising clinically relevant pathogens and human cells, to establish selective toxicity profiles in vitro, is critical. Further characterisation and discovery utilising artificial intelligence and computational screening approaches can accelerate future AMP nanomaterial development.
Assuntos
Peptídeos Antimicrobianos , Testes de Sensibilidade Microbiana , Polilisina , Humanos , Polilisina/farmacologia , Polilisina/química , Peptídeos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos/química , Antibacterianos/farmacologia , Antibacterianos/química , Eritrócitos/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Polímeros/farmacologia , Polímeros/química , Acinetobacter baumannii/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H2O2 production, but also NADPH down-regulation, intensifying redox damage to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harm to normal cells mainly due to metabolic vulnerability of the former. Once administered into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.
Assuntos
Nanopartículas , Polímeros , Animais , Camundongos , Humanos , Polímeros/química , Polímeros/farmacologia , Polímeros/administração & dosagem , Nanopartículas/química , Nanopartículas/administração & dosagem , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Glucose/metabolismo , Células RAW 264.7 , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Portadores de Fármacos/química , Proliferação de Células/efeitos dos fármacos , Reprogramação MetabólicaRESUMO
Photodynamic therapy (PDT) has emerged as a promising treatment for malignant tumours in recent decades due to its impressive spatiotemporal selectivity, minimal invasiveness, and few adverse effects. Despite these advancements, there remain significant challenges in effectively delivering photosensitizers to tumours and overcoming tumour hypoxia to maximize the therapeutic benefits of PDT. Ongoing research efforts are focused on developing innovative strategies to overcome the above-mentioned challenges, such as nanoplatforms and combination therapy approaches. Hence, reactive oxygen species (ROS)-responsive polymeric micelles are promising candidates to enhance the distribution and retention of photosensitizers within tumours. Additionally, efforts to alleviate tumour hypoxia may further improve the anti-tumour effects of PDT. In this study, we designed ROS-responsive polymeric micelles (TC@PTP) co-loaded with a Tapp-COF, a porphyrin derivative, and capsaicin for PDT of melanoma. These ROS-responsive nanocarriers, constructed from thioketal (TK)-linked amphiphilic di-block copolymers (PEG5K-TK-PLGA5K), could accumulate in the tumor microenvironment and release drugs under the action of ROS. Capsaicin, acting as a biogenic respiratory inhibitor, suppressed mitochondrial respiration and the hypoxia-inducible factor 1 (HIF-1) signaling pathway, thereby increasing oxygen levels at the tumour site. These PDT-triggered ROS-responsive nanoparticles effectively alleviated the tumour hypoxic microenvironment and enhanced anti-tumour efficacy. With superior biocompatibility and tumour-targeting abilities, the platform holds great promise for advancing anti-tumour combination therapy.
Assuntos
Micelas , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagem , Nanopartículas/química , Camundongos , Linhagem Celular Tumoral , Humanos , Hipóxia Tumoral/efeitos dos fármacos , Portadores de Fármacos/química , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/administração & dosagem , Microambiente Tumoral/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologiaRESUMO
Entomopathogenic fungi offer an ecologically sustainable and highly effective alternative to chemical pesticides for managing plant pests. However, the efficacy of mycoinsecticides in pest control suffers from environmental abiotic stresses, such as solar UV radiation and temperature fluctuations, which seriously hinder their practical application in the field. Herein, we discovered that the synthetic amphiphilic thermal-responsive polymers are able to significantly enhance the resistance of Metarhizium robertsii conidia against thermal and UV irradiation stresses. The thermosensitive polymers with extremely low cytotoxicity and good biocompatibility can be engineered onto the M. robertsii conidia surface by anchoring hydrophobic alkyl chains. Further investigations revealed that polymer supplementation remarkably augmented the capacity for penetration and the virulence of M. robertsii under heat and UV stresses. Notably, broad-spectrum entomopathogenic fungi can be protected by the polymers. The molecular mechanism was elucidated through exploring RNA sequencing and in vivo/vitro enzyme activity assays. This work provides a novel avenue for fortifying the resilience of entomopathogenic fungi, potentially advancing their practical application as biopesticides.
Assuntos
Metarhizium , Polímeros , Metarhizium/genética , Metarhizium/química , Metarhizium/efeitos da radiação , Polímeros/química , Polímeros/farmacologia , Temperatura Alta , Estresse Fisiológico , Raios Ultravioleta , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/efeitos da radiação , Animais , Controle Biológico de VetoresRESUMO
Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.
Assuntos
Movimento Celular , Hidrogéis , Raios Infravermelhos , Cicatrização , Cicatrização/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Humanos , Polímeros/química , Polímeros/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nanopartículas/química , Indóis/química , Indóis/farmacologiaRESUMO
For millions of years, barnacles and mussels have successfully adhered to wet rocks near tide-swept seashores. While the chemistry and mechanics of their underwater adhesives are being thoroughly investigated, an overlooked aspect of marine organismal adhesion is their ability to remove underlying biofilms from rocks and prepare clean surfaces before the deposition of adhesive anchors. Herein, we demonstrate that nonionic, coacervating synthetic polymers that mimic the physicochemical features of marine underwater adhesives remove â¼99% of Pseudomonas aeruginosa (P. aeruginosa) biofilm biomass from underwater surfaces. The efficiency of biofilm removal appears to align with the compositional differences between various bacterial biofilms. In addition, the surface energy influences the ability of the polymer to displace the biofilm, with biofilm removal efficiency decreasing for surfaces with lower surface energies. These synthetic polymers weaken the biofilm-surface interactions and exert shear stress to fracture the biofilms grown on surfaces with diverse surface energies. Since bacterial biofilms are 1000-fold more tolerant to common antimicrobial agents and pose immense health and economic risks, we anticipate that our unconventional approach inspired by marine underwater adhesion will open a new paradigm in creating antibiofilm agents that target the interfacial and viscoelastic properties of established bacterial biofilms.
Assuntos
Biofilmes , Pseudomonas aeruginosa , Propriedades de Superfície , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Biofilmes/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Aderência Bacteriana/efeitos dos fármacosRESUMO
A new easy protocol to functionalize the middle layer of commercial surgical face masks (FMs) with Zn and Cu oxides is proposed in order to obtain antibacterial personal protective equipment. Zinc and copper oxides were synthesized embedded in a polydopamine (PDA) shell as potential antibacterial agents; they were analyzed by XRD and TEM, revealing, in all the cases, the formation of metal oxide nanoparticles (NPs). PDA is a natural polymer appreciated for its simple and rapid synthesis, biocompatibility, and high functionalization; it is used in this work as an organic matrix that, in addition to stabilizing NPs, also acts as a diluent in the functionalization step, decreasing the metal loading on the polypropylene (PP) surface. The functionalized middle layers of the FMs were characterized by SEM, XRD, FTIR, and TXRF and tested in their bacterial-growth-inhibiting effect against Klebsiella pneumoniae and Staphylococcus aureus. Among all functionalizing agents, Cu2O-doped-ZnO NPs enclosed in PDA shell, prepared by an ultrasound-assisted method, showed the best antibacterial effect, even at low metal loading, without changing the hydrophobicity of the FM. This approach offers a sustainable solution by prolonging FM lifespan and reducing material waste.
Assuntos
Antibacterianos , Cobre , Indóis , Polímeros , Staphylococcus aureus , Óxido de Zinco , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Cobre/química , Staphylococcus aureus/efeitos dos fármacos , Nanopartículas Metálicas/química , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Máscaras , HumanosRESUMO
Most breast implants currently used in both reconstructive and cosmetic surgery have a silicone outer shell, which, despite much progress, remains susceptible to mechanical failure, infection, and foreign body response. This study shows that the durability and biocompatibility of breast implant-grade silicone can be enhanced by incorporating carbon nanomaterials of sp2 and sp3 hybridization into the polymer matrix and onto its surface. Plasma treatment of the implant surface can be used to modify platelet adhesion and activation to prevent thrombosis, postoperative infection, and inflammation disorders. The addition of 0.8% graphene flakes resulted in an increase in mechanical strength by 64% and rupture strength by around 77% when compared to pure silicone, whereas when nanodiamond (ND) was used as the additive, the mechanical strength was increased by 19.4% and rupture strength by 37.5%. Composites with a partially embedded surface layer of either graphene or ND showed superior antimicrobial activity and biocompatibility compared to pure silicone. All composite materials were able to sustain the attachment and growth of human dermal fibroblast, with the preferred growth noted on ND-coated surfaces when compared to graphene-coated surfaces. Exposure of these materials to hydrogen plasma for 5, 10, and 20 s led to substantially reduced platelet attachment on the surfaces. Hydrogen-treated pure silicone showed a decrease in platelet attachment for samples treated for 5-20 s, whereas silicone composite showed an almost threefold decrease in platelet attachment for the same plasma treatment times. The absence of platelet activation on the surface of composite materials suggests a significant improvement in hemocompatibility of the material.
Assuntos
Implantes de Mama , Humanos , Fibroblastos/efeitos dos fármacos , Fibroblastos/citologia , Adesividade Plaquetária/efeitos dos fármacos , Grafite/química , Grafite/farmacologia , Teste de Materiais , Polímeros/química , Polímeros/farmacologia , Propriedades de Superfície , Feminino , Silicones/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologiaRESUMO
PURPOSE: The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS-AA complex was examined. METHODS: After analyzing the CS-AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS-AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. RESULTS: Validating a systematic reduction in particle size, the following order was observed: CS > CS/AA simple mixture > CS-AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS-AA complex exhibits negligible surface charge. Additionally, Fourier-transform infrared spectroscopy (FT-IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS-AA complex. Subsequently, the water-holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS-Q complex: 40.6% (1 h), 20.5% (2 h), and 18.7% (4 h) compared to glycerin. Similarly, the CS-R complex demonstrated enhancements of 50.2% (1 h), 37.5% (2 h), and 33% (4 h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS-Q complex and CS-R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS-Q complex and CS-R complex showed a significant increase in moisture levels after 4 weeks of application. CONCLUSION: In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well-known moisturizing agent, confirmed that the CS-AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS-AA complex is a more effective ingredient than CS or AA alone in terms of efficacy.
Assuntos
Sulfatos de Condroitina , Cosméticos , Perda Insensível de Água , Humanos , Animais , Suínos , Perda Insensível de Água/efeitos dos fármacos , Cosméticos/farmacologia , Cosméticos/química , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacologia , Feminino , Pele/química , Pele/efeitos dos fármacos , Pele/metabolismo , Adulto , Aminoácidos/química , Aminoácidos/farmacologia , Emolientes/farmacologia , Emolientes/administração & dosagem , Emolientes/química , Polímeros/farmacologia , Polímeros/química , Glutamina/farmacologia , PolieletrólitosRESUMO
The antibacterial efficacy and specificity of lytic bacteriophages (phages) make them promising therapeutics for treatment of multidrug-resistant bacterial infections. Restricted penetration of phages through the protective matrix of biofilms, however, may limit their efficacy against biofilm infections. Here, engineered polymers were used to generate noncovalent phage-polymer nanoassemblies (PPNs) that penetrate bacterial biofilms and kill resident bacteria. Phage K, active against multiple strains of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), was assembled with cationic poly(oxanorbornene) polymers into PPNs. The PPNs retained phage infectivity, while demonstrating enhanced biofilm penetration and killing relative to free phages. PPNs achieved 3-log10 bacterial reduction (â¼99.9%) against MRSA biofilms in vitro. PPNs were then incorporated into Poloxamer 407 (P407) hydrogels and applied onto in vivo wound biofilms, demonstrating controlled and sustained release. Hydrogel-incorporated PPNs were effective in a murine MRSA wound biofilm model, showing a 1.5-log10 reduction in bacterial load compared to a 0.5 log reduction with phage K in P407 hydrogel. Overall, this work showcases the therapeutic potential of phage K engineered with cationic polymers for treating wound biofilm infections.
Assuntos
Antibacterianos , Biofilmes , Staphylococcus aureus Resistente à Meticilina , Polímeros , Biofilmes/efeitos dos fármacos , Animais , Camundongos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/virologia , Polímeros/química , Polímeros/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/terapia , Infecção dos Ferimentos/tratamento farmacológico , Bacteriófagos , Hidrogéis/química , Hidrogéis/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/virologia , Staphylococcus aureus/fisiologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/terapia , Infecções Estafilocócicas/tratamento farmacológico , Nanoestruturas/químicaRESUMO
The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-ß receptor, TGF-ßR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-ß (TGF-ß) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.
Assuntos
Neoplasias do Colo , Verde de Indocianina , Animais , Camundongos , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Neoplasias do Colo/tratamento farmacológico , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Verde de Indocianina/uso terapêutico , Indóis/química , Indóis/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Apoptose/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Carbonato de Cálcio/química , Carbonato de Cálcio/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Humanos , Proliferação de Células/efeitos dos fármacos , Nanopartículas Multifuncionais/químicaRESUMO
Reducing unnecessary blood loss in hemostasis is a major challenge for traditional hemostatic materials due to uncontrolled blood absorption. Tuning the hydrophilic and hydrophobic properties of hemostatic materials provides a road to reduce blood loss. Here, we developed a superhydrophobic aerogel that enabled remarkably reduced blood loss. The aerogel was fabricated with polydopamine-coated and fluoroalkyl chain-modified bacterial cellulose via a directional freeze-drying method. Primarily, the hydrophobic feature prevented blood from uncontrolled absorption by the material and overflowing laterally. Additionally, the aerogel had a dense network of channels that allowed it to absorb water from blood due to the capillary effect, and fluoroalkyl chains trapped the blood cells entering the channels to form a compact barrier via hydrophobic interaction at the bottom of the aerogel, causing quick fibrin generation and blood coagulation. The animal experiments reveal that the aerogel reduced the hemostatic time by 68% and blood loss by 87 wt % compared with QuikClot combat gauze. The study demonstrates the superiority of superhydrophobic aerogels for hemostasis and provides new insights into the development of hemostatic materials.
Assuntos
Celulose , Hemostasia , Hemostáticos , Interações Hidrofóbicas e Hidrofílicas , Nanofibras , Celulose/química , Celulose/farmacologia , Animais , Nanofibras/química , Hemostáticos/química , Hemostáticos/farmacologia , Hemostasia/efeitos dos fármacos , Géis/química , Polímeros/química , Polímeros/farmacologia , Camundongos , Humanos , Coagulação Sanguínea/efeitos dos fármacos , Indóis/químicaRESUMO
Biomedical-device-associated infection (BAI) is undoubtedly a major concern and a serious challenge in modern medicine. Therefore, the development of biomedical materials that are capable of resisting or killing bacteria is of great importance. In this work, a croconaine-functionalized polymer with antifouling and near-infrared (NIR) photothermal bactericidal properties was prepared and facilely modified on polypropylene (PP) to combat medical device infections. Croconaine dye is elaborately modified as a "living" initiator, termed CR-4EBiB, for preparing amphiphilic block polymers by atom transfer radical polymerization (ATRP). In the formed polymer coating, the hydrophobic block can strongly adhere to the surface of the PP substrate, whereas the hydrophilic block is located on the outer layer by solvent-induced resistance to bacterial adhesion. Under the irradiation of an NIR laser (808 nm), the croconaine dye in the coating achieved maximum conversion of light to heat to effectively kill E. coli, S. aureus, and methicillin-resistant Staphylococcus aureus (MRSA). This work provides a facile and promising strategy for the development of implantable antibacterial biomedical materials.
Assuntos
Antibacterianos , Escherichia coli , Raios Infravermelhos , Staphylococcus aureus Resistente à Meticilina , Polipropilenos , Polipropilenos/química , Polipropilenos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Propriedades de Superfície , Polímeros/química , Polímeros/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Incrustação Biológica/prevenção & controleRESUMO
Background: Polymeric denture materials can be susceptible to colonization by oral microorganisms. Zein-coated magnesium oxide nanoparticles (zMgO NPs) demonstrate antimicrobial activity. The aim of this study was to investigate the antimicrobial effect and adherence of different oral microorganisms on hybrid polymeric denture materials incorporated with zMgO NPs. Methods: Five types of polymeric denture materials were used. A total of 480 disc-shaped specimens were divided by material type (n=96/grp), then subdivided by zMgO NPs concentration: control with no nanoparticles and other groups with zMgO NPs concentrations of 0.3%, 0.5% and 1% by weight. Characterization of the polymeric denture materials incorporating zMgO NPs was done, and the antimicrobial activity of all groups was tested against four types of microorganisms: 1) Streptococcus mutans, 2) Staphylococcus aureus, 3) Enterococcus faecalis and 4) Candida albicans. The samples underwent an adherence test and an agar diffusion test. Experiments were done in triplicates. Results: The characterization of the hybrid samples revealed variation in the molecular composition, as well as a uniform distribution of the zMgO NPs in the polymeric denture materials. All hybrid polymeric denture materials groups induced a statistically significant antimicrobial activity, while the control groups showed the least antimicrobial activity. The agar diffusion test revealed no release of the zMgO NPs from the hybrid samples, indicating the NPs did not seep out of the matrix. Conclusion: The zMgO NPs were effective in reducing the adherence of the tested microorganisms and enhancing the antimicrobial activity of the polymeric denture materials. This antimicrobial effect with the polymeric dentures could aid in resisting microbial issues such as denture stomatitis.
Assuntos
Anti-Infecciosos , Candida albicans , Staphylococcus aureus , Streptococcus mutans , Zeína , Zeína/química , Zeína/farmacologia , Candida albicans/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Óxido de Magnésio/química , Óxido de Magnésio/farmacologia , Nanopartículas/química , Enterococcus faecalis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Humanos , Materiais Dentários/farmacologia , Materiais Dentários/química , Dentaduras/microbiologia , Polímeros/química , Polímeros/farmacologiaRESUMO
Polydopamine is a versatile and modifiable polymer, known for its excellent biocompatibility and adhesiveness. It can also be engineered into a variety of nanoparticles and biomaterials for drug delivery, functional modification, making it an excellent choice to enhance the prevention and treatment of orthopedic diseases. Currently, the application of polydopamine biomaterials in orthopedic disease prevention and treatment is in its early stages, despite some initial achievements. This article aims to review these applications to encourage further development of polydopamine for orthopedic therapeutic needs. We detail the properties of polydopamine and its biomaterial types, highlighting its superior performance in functional modification on nanoparticles and materials. Additionally, we also explore the challenges and future prospects in developing optimal polydopamine biomaterials for clinical use in orthopedic disease prevention and treatment.
Assuntos
Materiais Biocompatíveis , Indóis , Polímeros , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Humanos , Animais , Nanopartículas/química , Sistemas de Liberação de MedicamentosRESUMO
Bacterial biofilms represent an escalating global health concern with the proliferation of drug resistance and hospital-acquired infections annually. Numerous strategies are under exploration to combat biofilms and preempt the development of antibacterial resistance. Among these, mechanical disruption of biofilms and enclosed bacteria presents a promising avenue, aiming to induce membrane permeabilization and consequent lethal damage. Herein, we introduce a hemithioindigo (HTI) motor activated by visible light, capable of disrupting sessile bacteria when integrated into a polymeric vesicle carrier. Under visible light, bacteria exhibited a notable outer membrane permeability, reduced membrane fluidity, and diminished viability following mechanical drilling. Moreover, various genetic responses pertaining to the cell envelope were examined via qRT-PCR, alongside the activation of a self-lysis mechanism associated with phage stress, which was coupled with increases in quorum sensing, demonstrating a potential self-lysis cascade from within. The multifaceted mechanisms of action, coupled with the energy efficiency of mechanical damage, underscore the potential of this system in addressing the challenges posed by pathogenic biofilms.
Assuntos
Biofilmes , Luz , Percepção de Quorum , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacosRESUMO
Balancing biocompatibility and drug-loading efficiency in nanoparticles presents a significant challenge. In this study, we describe the facile fabrication of poly (acrylic acid)-mesoporous zinc phosphate/polydopamine (PAA-mZnP/PDA) Janus nanoparticles (JNPs). The PDA half-shell itself can serve as a photothermal agent for photothermal therapy (PTT), as well as to offers sites for polyethylene glycol (PEG) to enhance biocompatibility. Concurrently, the mesoporous ZnP core allows high loading of doxorubicin (DOX) for chemotherapy and the Cy5.5 dye for fluorescence imaging. The resultant PAA-mZnP/PDA-PEG JNPs exhibit exceptional biocompatibility, efficient drug loading (0.5 mg DOX/1 mg JNPs), and dual pH/NIR-responsive drug release properties. We demonstrate the JNPs' satisfactory anti-cancer efficacy, highlighting the synergistic effects of chemotherapy and PTT. Furthermore, the potential for synergistic fluorescence imaging-guided chemo-phototherapy in cancer treatment is illustrated. Thus, this work exemplifies the development of biosafe, multifunctional JNPs for advanced applications in cancer theranostics. STATEMENT OF SIGNIFICANCE: Facile fabrication of monodispersed nanomedicine with multi-cancer killing modalities organically integrated is nontrivial and becomes more challenging under the biocompatibility requirement that is necessary for the practical applications of nanomedicines. In this study, we creatively designed PAA-mZnP/PDA JNPs and fabricated them under mild conditions. Our method reliably yields uniform JNPs with excellent monodispersity. To maximize functionalities, we achieve fourfold advantages including efficient drug/fluorescent dye loading, PTT, pH/NIR dual-responsive properties, and optimal biocompatibility. The as-fabricated JNPs exhibit satisfactory anti-cancer performance both in vitro and in vivo, and demonstrate the potential of JNPs in fluorescence imaging-guided synergistic cancer chemo-phototherapy. Overall, our research establishes a pathway in versatile inorganic/polymer JNPs for enhanced cancer diagnosis and therapy.
Assuntos
Resinas Acrílicas , Doxorrubicina , Portadores de Fármacos , Indóis , Nanopartículas , Terapia Fototérmica , Polímeros , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Indóis/química , Indóis/farmacologia , Polímeros/química , Polímeros/farmacologia , Nanopartículas/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Humanos , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Animais , Raios Infravermelhos , Porosidade , Camundongos , Compostos de Zinco/química , Linhagem Celular Tumoral , Células HeLaRESUMO
The characteristics of dopamine self-polymerization were used to cover the nano-titanium dioxide (TiO2) surface and produce nano-titanium dioxide-polydopamine (TiO2-PDA). The reducing nature of dopamine was then used to reduce silver nitrate to silver elemental particles on the modified nano-titanium dioxide: The resulting TiO2-PDA-Ag nanoparticles were used as antimicrobial agents. Finally, the antibacterial agent was mixed with silicone to obtain an antibacterial silicone composite material. The composition and structure of antibacterial agents were analyzed by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron energy spectroscopy, and X-ray diffraction. Microscopy and the antibacterial properties of the silicone antibacterial composites were studied as well. The TiO2-PDA-Ag antimicrobial agent had good dispersion versus nano-TiO2. The three were strongly combined with obvious characteristic peaks. The antibacterial agents were evenly dispersed in silicone, and the silicone composite has excellent antibacterial properties. Bacillus subtilis (B. subtilis) adhesion was reduced from 246 × 104 cfu/cm2 to 2 × 104 cfu/cm2, and colibacillus (E. coli) reduced from 228 × 104 cfu/cm2 leading to bacteria-free adhesion.