Inhalable Bottlebrush Polymer Bioconjugates as Vectors for Efficient Pulmonary Delivery of Oligonucleotides.
Inhalable Bottlebrush Polymer Bioconjugates as Vectors for Efficient Pulmonary Delivery of Oligonucleotides.
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DOI：
10.1021/acsnano.3c08660
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发表时间：
2024-01-09
期刊：
影响因子：
17.1
通讯作者：
Zhang, Ke
中科院分区：
文献类型：
--
作者：
Fang, Yang;Cai, Jiansong;Ren, Mengqi;Zhong, Tongtong;Wang, Dali;Zhang, Ke
关键词：
Antisense oligonucleotides hold therapeutic promise for various lung disorders, but their efficacy is limited by suboptimal delivery. To address this challenge, we explored the use of inhaled bottlebrush polymer–DNA conjugates, named pacDNA, as a delivery strategy. Inhaled pacDNA exhibits superior mucus penetration, achieving a uniform and sustained lung distribution in mice. Targeting the 5′ splice site of an aberrant enhanced green fluorescence protein (EGFP) pre-mRNA in EGFP-654 mice, inhaled pacDNA more efficiently corrects splicing than a B-peptide conjugate and restores EGFP expression in the lung. Additionally, in an orthotopic NCI-H358 non-small-cell lung tumor mouse model, inhaled pacDNA targeting wild-type KRAS mRNA effectively suppresses KRAS expression and inhibits lung tumor growth, requiring a substantially lower dosage compared to intravenously injected pacDNA. These findings demonstrate the potential of bottlebrush polymer–DNA conjugates as a promising agent for enhanced oligonucleotide therapy in the lung and advancing the treatment landscape for lung disorders.
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DOI：
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发表时间：
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期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
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作者：
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DOI：
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期刊：
Angewandte Chemie (International ed. in English)
影响因子：
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Suk JS
影响因子：
16.1
作者：
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通讯作者：
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DOI：
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发表时间：
2016-06
期刊：
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影响因子：
--
作者：
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通讯作者：
Hanes J
DOI：
10.1073/pnas.1502281112
发表时间：
2015-07-14
影响因子：
11.1
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Suk, Jung Soo