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Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis.


ABSTRACT: Elimination of airway inflammatory cells is essential for asthma control. As Bcl-2 protein is highly expressed on the mitochondrial outer membrane in inflammatory cells, we chose a Bcl-2 inhibitor, ABT-199, which can inhibit airway inflammation and airway hyperresponsiveness by inducing inflammatory cell apoptosis. Herein, we synthesized a pH-sensitive nanoformulated Bcl-2 inhibitor (Nf-ABT-199) that could specifically deliver ABT-199 to the mitochondria of bronchial inflammatory cells. The proof-of-concept study of an inflammatory cell mitochondria-targeted therapy using Nf-ABT-199 was validated in a mouse model of allergic asthma. Nf-ABT-199 was proven to significantly alleviate airway inflammation by effectively inducing eosinophil apoptosis and inhibiting both inflammatory cell infiltration and mucus hypersecretion. In addition, the nanocarrier or Nf-ABT-199 showed no obvious influence on cell viability, airway epithelial barrier and liver function, implying excellent biocompatibility and with non-toxic effect. The nanoformulated Bcl-2 inhibitor Nf-ABT-199 accumulates in the mitochondria of inflammatory cells and efficiently alleviates allergic asthma.

SUBMITTER: Tian BP 

PROVIDER: S-EPMC6561093 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis.

Tian Bao-Ping BP   Li Fangyuan F   Li Ruiqing R   Hu Xi X   Lai Tian-Wen TW   Lu Jingxiong J   Zhao Yun Y   Du Yang Y   Liang Zeyu Z   Zhu Chen C   Shao Wei W   Li Wen W   Chen Zhi-Hua ZH   Sun Xiaolian X   Chen Xiaoyuan X   Ying Songmin S   Ling Daishun D   Shen Huahao H  

Biomaterials 20180618


Elimination of airway inflammatory cells is essential for asthma control. As Bcl-2 protein is highly expressed on the mitochondrial outer membrane in inflammatory cells, we chose a Bcl-2 inhibitor, ABT-199, which can inhibit airway inflammation and airway hyperresponsiveness by inducing inflammatory cell apoptosis. Herein, we synthesized a pH-sensitive nanoformulated Bcl-2 inhibitor (Nf-ABT-199) that could specifically deliver ABT-199 to the mitochondria of bronchial inflammatory cells. The proo  ...[more]

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