RESUMO
Most immunomodulatory materials (e.g., vaccine adjuvants such as alum) modulate adaptive immunity, and yet little effort has focused on developing materials to regulate innate immunity, which get mentioned only when inflammation affects the biocompatibility of biomaterials. Traditionally considered as short-lived effector cells from innate immunity primarily for the clearance of invading microorganisms without specificity, neutrophils exhibit a key role in launching and shaping the immune response. Here we show that the incorporation of unnatural amino acids into a well-known chemoattractant-N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-offers a facile approach to create a de novo, multifunctional chemoattractant that self-assembles to form supramolecular nanofibrils and hydrogels. This de novo chemoattractant not only exhibits preserved cross-species chemoattractant activity to human and murine neutrophils, but also effectively resists proteolysis. Thus, its hydrogel, in vivo, releases the chemoattractant and attracts neutrophils to the desired location in a sustainable manner. As a novel and general approach to generate a new class of biomaterials for modulating innate immunity, this work offers a prolonged acute inflammation model for developing various new applications.
Assuntos
Fatores Quimiotáticos/química , Hidrogéis/química , Fatores Imunológicos/química , N-Formilmetionina Leucil-Fenilalanina/química , Neutrófilos/imunologia , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Fatores Quimiotáticos/imunologia , Reações Cruzadas , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Fatores Imunológicos/farmacologia , Imunomodulação , Inflamação/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reologia , Relação Estrutura-AtividadeRESUMO
Here we report the first example of using ß-galactosidase to trigger the formation of cell compatible, supramolecular nanofibers, which ultimately may lead to a new approach for the development of soft nanotechnology.
Assuntos
Hidrogel de Polietilenoglicol-Dimetacrilato/química , Nanofibras/química , beta-Galactosidase/metabolismo , Sítios de Ligação , Escherichia coli/enzimologia , Concentração de Íons de Hidrogênio , Nanofibras/ultraestruturaRESUMO
The hydrolysis of the carboxylic ester bond, by a base or catalyzed by an enzyme under weak basic conditions, serves as the only path to obtain a novel anisotropic supramolecular hydrogel that is stable over a wide pH range. This result not only expands the molecular scope of supramolecular hydrogelators but also illustrates the design principles for creating pH-stable supramolecular soft materials.