RESUMO
Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework-8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface-grafted cyclo(Arg-Gly-Asp-d-Phe-Lys) after intravitreal injection. The excessive H2 O2 in the CNV microenvironment is catalyzed by catalase-like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti-inflammatory and anti-angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia-inducible factor-1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.
Assuntos
Neovascularização de Coroide , Nanoestruturas , Fotoquimioterapia , Porfirinas , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Nanomedicina , Porfirinas/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismoRESUMO
Corneal infection is an important cause of corneal damage and vision loss. In this work, polyhydroxy antibiotics were grafted onto polymer brush-modified contact lenses through dynamic chemical bonds between polyphenolic hydroxyls and phenylboronic acid. Both in vitro and in vivo antibacterial tests demonstrated great promise in the prevention of bacterial keratitis, which could be attributed to the enhanced retention time and drug bioavailability.
Assuntos
Antibacterianos/metabolismo , Lentes de Contato , Córnea/metabolismo , Ceratite/metabolismo , Polímeros/metabolismo , Infecções Estafilocócicas/metabolismo , Animais , Antibacterianos/administração & dosagem , Córnea/efeitos dos fármacos , Córnea/microbiologia , Concentração de Íons de Hidrogênio , Ceratite/tratamento farmacológico , Ceratite/prevenção & controle , Polímeros/administração & dosagem , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/prevenção & controleRESUMO
Endophthalmitis, derived from the infections of pathogens, is a common complication during the use of ophthalmology-related biomaterials and after ophthalmic surgery. Herein, aiming at efficient photodynamic therapy (PDT) of bacterial infections and biofilm eradication of endophthalmitis, a pH-responsive zeolitic imidazolate framework-8-polyacrylic acid (ZIF-8-PAA) material is constructed for bacterial infection-targeted delivery of ammonium methylbenzene blue (MB), a broad-spectrum photosensitizer antibacterial agent. Polyacrylic acid (PAA) is incorporated into the system to achieve higher pH responsiveness and better drug loading capacity. MB-loaded ZIF-8-PAA nanoparticles are modified with AgNO3 /dopamine for in situ reduction of AgNO3 to silver nanoparticles (AgNPs), followed by a secondary modification with vancomycin/NH2 -polyethylene glycol (Van/NH2 -PEG), leading to the formation of a composite nanomaterial, ZIF-8-PAA-MB@AgNPs@Van-PEG. Dynamic light scattering, transmission electron microscopy, and UV-vis spectral analysis are used to explore the nanoparticles synthesis, drug loading and release, and related material properties. In terms of biological performance, in vitro antibacterial studies against three kinds of bacteria, i.e., Escherichia coli, Staphylococcus aureus, and methicillin-resistant S. aureus, suggest an obvious superiority of PDT/AgNPs to any single strategy. Both in vitro retinal pigment epithelium cellular biocompatibility experiments and in vivo mice endophthalmitis models verify the biocompatibility and antibacterial function of the composite nanomaterials.
Assuntos
Sistemas de Liberação de Medicamentos , Endoftalmite/tratamento farmacológico , Imidazóis/química , Fotoquimioterapia , Zeolitas/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Animais , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Humanos , Imidazóis/síntese química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Estruturas Metalorgânicas/química , Camundongos , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Coelhos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/citologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/ultraestrutura , Propriedades de Superfície , Vancomicina/farmacologia , Zeolitas/síntese químicaRESUMO
In recent decades, bacterial and viral infections and chronic inflammatory response have emerged as important causes of cancer. Also, infections remain a significant cause of morbidity and mortality in cancer patients. In this work, carboxymethyl chitosan nanoparticles (CMC NPs) were synthesized in a facile and green way and further combined with ammonium methylbenzene blue (MB) as a cross-linking agent as well as a fluorescent molecule and a photosensitizer for self-imaging photodynamic therapy (PDT). The obtained CMC-MB NPs exhibited an apparent pH-responsive release behavior of MB, which was released for a prolonged period in a simulated physiological environment (pH 7.4) for more than 15 days and the time reduced to only 3.5 h in acidic conditions (pH 5.5). When irradiated by a 650 nm laser at 202 mW/cm2 for 5 min, the CMC-MB NPs showed efficient bactericidal and biofilm eradication properties as well as suppression of tumor cell growth in a similar acidified microenvironment. Furthermore, in an in vivo rabbit wound bacterial infection model, the rapid sterilization of CMC-MB NPs played a crucial role in bacterial infections, inflammation inhibition, and wound healing. As a PDT treatment against cancer, the CMC-MB NPs also exhibited an efficient antitumor therapeutic effect in a subcutaneous tumor mice model.