한빛사논문
- 조회854
Daiqin Chen#,[a, b] Shuai Liu#,[c] Dinghao Chen,[a, d] Jinhao Liu,[a, d] Jerry Wu,[a] Han Wang,[d] Yun Su,[a, b] Gijung Kwak,[a, b] Xinyuan Zuo,[a, d] Divya Rao,[a, d] Honggang Cui,[d] Chunying Shu*[c] and Jung Soo Suk*[a, b, d]
[a] Dr. D. Chen, D. Chen, J. Liu, J. Wu, Dr. Y. Su, D. Rao, Dr. G. Kwak, X. Zuo and Prof. J. Suk
The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins, Baltimore, MD, USA
[b] Dr. D. Chen, Dr. Y. Su, Dr. G. Kwak, and Prof. J. Suk
Department of Ophthalmology, Johns Hopkins University, Baltimore, MD, USA
[c] S. Liu and Prof. C. Shu
Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing, PR China
[d] H. Wang, D. Rao, Prof. H. Cui and Prof. J. Suk
Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA
#These two authors contributed equally.
*Corresponding author.
Abstract
Inhaled gene therapy poses a unique potential of curing chronic lung diseases which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically-relevant gene transfer efficacy in the lung thus far due to the presence of numerous biological delivery barriers. Here, we introduce a simple combinatorial approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo . We have endowed tetra(piperazino)fullerene epoxide (TPFE)-based nanoparticles with non-adhesive surface polyethylene glycol (PEG) coatings, thereby enabling the nanoparticles to percolate the airway mucus gel layer and obviate phagocytic uptake by alveolar macrophages. In parallel, we have utilized a hypotonic vehicle to facilitate endocytic uptake of the PEGylated nanoparticles by lung parenchymal cells via the osmotically-driven regulatory volume decrease (RVD) mechanism. We demonstrate here that this two-pronged delivery strategy provides safe, wide-spread and high-level transgene expression in the lungs of both healthy mice and mice with chronic lung diseases characterized by reinforced delivery barriers.
논문정보
- Research article
- 2021년 04월 (BRIC 등록일 2021-05-28)
- 국외 연구진
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