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ACS Appl Mater Interfaces ; 13(50): 59662-59672, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34894655

RESUMO

Hydroxyapatite (HAP) has been formulated as adjuvants in vaccines for human use. However, the optimal properties required for HAP nanoparticles to elicit adjuvanticity and the underlying immunopotentiation mechanisms have not been fully elucidated. Herein, a library of HAP nanorods and nanospheres was synthesized to explore the effect of the particle shape and aspect ratio on the immune responses in vitro and adjuvanticity in vivo. It was demonstrated that long aspect ratio HAP nanorods induced a higher degree of cell membrane depolarization and subsequent uptake, and the internalized particles elicited cathepsin B release and mitochondrial reactive oxygen species generation, which further led to pro-inflammatory responses. Furthermore, the physicochemical property-dependent immunostimulation capacities were correlated with their humoral responses in a murine hepatitis B surface antigen immunization model, with long aspect ratio HAP nanorods inducing higher antigen-specific antibody productions. Importantly, HAP nanorods significantly up-regulated the IFN-γ secretion and CD107α expression on CD8+ T cells in immunized mice. Further mechanistic studies demonstrated that HAP nanorods with defined properties exerted immunomodulatory effects by enhanced antigen persistence and immune cell recruitments. Our study provides a rational design strategy for engineered nanomaterial-based vaccine adjuvants.


Assuntos
Adjuvantes Imunológicos/farmacologia , Materiais Biocompatíveis/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Durapatita/farmacologia , Antígenos de Superfície da Hepatite B/imunologia , Nanopartículas/química , Adjuvantes Imunológicos/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Durapatita/síntese química , Durapatita/química , Imunidade/efeitos dos fármacos , Interferon gama/biossíntese , Proteína 1 de Membrana Associada ao Lisossomo/genética , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Teste de Materiais
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