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Nanoscale Porphyrin Metal-Organic Frameworks Deliver siRNA for Alleviating Early Pulmonary Fibrosis in Acute Lung Injury.


ABSTRACT: Acute lung injury (ALI) has high mortality and still lacks novel and efficient therapies. Zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) are highly expressed in the early stage of ALI and are positively correlated with the progression of pulmonary fibrosis. Herein, we developed a nanoscale Zr(IV)-based porphyrin metal-organic (ZPM) framework to deliver small interfering ZEB1/2 (siZEB1/2) to alleviate early pulmonary fibrosis during ALI. This pH-responsive nano-ZPM system could effectively protect siRNAs during lung delivery until after internalization and rapidly trigger siRNA release under the mildly acidic environment of the endo/lysosome (pH 4.0-6.5) for transfection and gene silencing. Furthermore, the in vivo studies confirmed that this nano-ZPM system could anchor in inflamed lungs. Moreover, the ZEB1/2 silencing led to increased E-cadherin and decreased α-SMA levels. Overall, the nano-ZPM system was an excellent non-viral vector system to deliver siRNAs to alleviate early pulmonary fibrosis during ALI.

SUBMITTER: Weng C 

PROVIDER: S-EPMC9339993 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Nanoscale Porphyrin Metal-Organic Frameworks Deliver siRNA for Alleviating Early Pulmonary Fibrosis in Acute Lung Injury.

Weng Changmei C   Li Guanhua G   Zhang Dongdong D   Duan Zhaoxia Z   Chen Kuijun K   Zhang Jieyuan J   Li Tao T   Wang Jianmin J  

Frontiers in bioengineering and biotechnology 20220718


Acute lung injury (ALI) has high mortality and still lacks novel and efficient therapies. Zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) are highly expressed in the early stage of ALI and are positively correlated with the progression of pulmonary fibrosis. Herein, we developed a nanoscale Zr(IV)-based porphyrin metal-organic (ZPM) framework to deliver small interfering ZEB1/2 (siZEB1/2) to alleviate early pulmonary fibrosis during ALI. This pH-responsive nano-ZPM system could effectively p  ...[more]

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