期刊
BIOMATERIALS SCIENCE
卷 9, 期 13, 页码 4746-4754出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm00481f
关键词
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资金
- National Key Research and Development Program of China [2019YFA0111300]
- Science and Technology Program of Guangzhou [2017040220179, 202102010225, 202102010217]
- National Natural Science Foundation of China [51903256, 21907113, 32001012]
- Guangdong Provincial Science and Technology Program (International Scientific Cooperation) [2018A050506035]
- Guangdong Provincial Pearl River Talents Program [2019QN01Y131]
Delayed neutrophil apoptosis has been associated with acute lung injury. Venetoclax, a Bcl-2 inhibitor, has shown potential in improving clinical outcomes of acute lung injury but faces delivery challenges due to its water insolubility. Utilizing an amphiphilic polymer-based nanoparticle, Nf-venetoclax was able to increase neutrophil apoptosis in vivo, demonstrating effective therapy for acute lung injury.
Delayed neutrophil apoptosis has been proved to be closely associated with acute lung injury. A Bcl-2 inhibitor, venetoclax, can improve the clinical outcome of acute lung injury based on its pro-apoptotic effect. However, pulmonary delivery of free venetoclax is hindered by its water insolubility, which results in limited bioavailability and pharmacological effects. An amphipathic polymer-based nanodelivery system has been extensively used to improve the delivery of this insoluble drug and enhance its bioavailability. In this study, an amphiphilic poly(ethylene glycol) modified poly(alpha-lipoic acid) nanoparticle with an extended lung tissue-resident time was utilized to deliver venetoclax. Compared to free venetoclax, the nanoformulated venetoclax (Nf-venetoclax) presented better efficacy for acute lung injury through increasing neutrophil apoptosis in vivo. In addition, a stronger pro-apoptotic effect of Nf-venetoclax was also demonstrated in vitro. Our study provides encouraging evidence that Nf-venetoclax exhibits effective therapy for acute lung injury.
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