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Gold nanoparticle-capped mesoporous silica-based H2O2-responsive controlled release system for Alzheimer's disease treatment.
Yang, Licong; Yin, Tiantian; Liu, Yanan; Sun, Jing; Zhou, Yanhui; Liu, Jie.
Afiliação
  • Yang L; Department of Chemistry, Jinan University, Guangzhou 510632, PR China.
  • Yin T; Department of Chemistry, Jinan University, Guangzhou 510632, PR China.
  • Liu Y; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong.
  • Sun J; Department of Chemistry, Jinan University, Guangzhou 510632, PR China.
  • Zhou Y; Department of Chemistry, Jinan University, Guangzhou 510632, PR China.
  • Liu J; Department of Chemistry, Jinan University, Guangzhou 510632, PR China. Electronic address: tliuliu@jnu.edu.cn.
Acta Biomater ; 46: 177-190, 2016 12.
Article em En | MEDLINE | ID: mdl-27619837
Metal ions promote Alzheimer's disease (AD) pathogenesis by accelerating amyloid-ß (Aß) aggregation and inducing formation of neurotoxic reactive oxygen species (ROS) such as hydrogen peroxide (H2O2). Although metal chelators can block these effects, their therapeutic potential is marred by their inability to cross the blood-brain barrier (BBB) and by their non-specific interactions with metal ions necessary for normal cellular processes, which could result in adverse side effects. To overcome these limitations, we created a novel gold nanoparticle-capped mesoporous silica (MSN-AuNPs) based H2O2-responsive controlled release system for targeted delivery of the metal chelator CQ. In this system, CQ is released only upon exposure to conditions in which H2O2 levels are high, such as those in Aß plaques. The conjugation of AuNPs on the surface of MSN did not affect their ability to cross the BBB. The AuNPs also help in decrease the Aß self-assembly, due to this, MSN-CQ-AuNPs were more efficient than MSN-CQ in inhibiting Cu2+-induced Aß40 aggregation. Furthermore, MSN-CQ-AuNPs reduced the cell membrane disruption, microtubular defects and ROS-mediated apoptosis induced by Aß40-Cu2+ complexes. The high BBB permeability, efficient anti-Aß aggregation, and good biocompatibility of MSN-CQ-AuNPs, together with the specific conditions necessary for its release of CQ, demonstrate its potential for future biomedical applications. STATEMENT OF SIGNIFICANCE: Due to the low ability to cross the blood-brain barrier (BBB) and non-specific interactions with metal ions necessary for normal cellular processes of metal chelator or Aß inhibitors, we created a novel gold nanoparticle-capped mesoporous silica (MSN-AuNPs)-based H2O2-responsive controlled release system for targeted delivery of the metal chelator CQ and AuNPs (Aß inhibitor). In this system, CQ and AuNPs are released only upon exposure to conditions in which H2O2 levels are high, such as those in Aß plaques. The AuNPs on the surface of MSN also help in decrease the Aß self-assembly, due to this, MSN-CQ-AuNPs were more efficient than MSN-CQ in inhibiting Cu2+-induced Aß40 aggregation. Furthermore, MSN-CQ-AuNPs reduced the cell membrane disruption, microtubular defects and ROS-mediated apoptosis induced by Aß40-Cu2+ complexes. Our data suggest that this controlled release system may have widespread application in the field of medicine for Alzheimer's disease.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Nanopartículas Metálicas / Doença de Alzheimer / Ouro / Peróxido de Hidrogênio Limite: Animals Idioma: En Revista: Acta Biomater Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 6_ODS3_enfermedades_notrasmisibles Base de dados: MEDLINE Assunto principal: Nanopartículas Metálicas / Doença de Alzheimer / Ouro / Peróxido de Hidrogênio Limite: Animals Idioma: En Revista: Acta Biomater Ano de publicação: 2016 Tipo de documento: Article