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聚(酯胺)介导的、气溶胶递送的Akt1小干扰RNA抑制肺癌发生。

Poly(ester amine)-mediated, aerosol-delivered Akt1 small interfering RNA suppresses lung tumorigenesis.

作者信息

Xu Cheng-Xiong, Jere Dhananjay, Jin Hua, Chang Seung-Hee, Chung Youn-Sun, Shin Ji-Young, Kim Ji-Eun, Park Sung-Jin, Lee Yong-Hoon, Chae Chan-Hee, Lee Kee Ho, Beck George R, Cho Chong-Su, Cho Myung-Haing

机构信息

Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.

出版信息

Am J Respir Crit Care Med. 2008 Jul 1;178(1):60-73. doi: 10.1164/rccm.200707-1022OC. Epub 2008 Feb 28.

DOI:10.1164/rccm.200707-1022OC
PMID:18310482
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2441927/
Abstract

RATIONALE

The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for the development of novel therapeutic options. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.

OBJECTIVES

To demonstrate the feasibility and emphasize the importance of noninvasive aerosol delivery of Akt1 small interfering RNA (siRNA) as an effective and selective option for lung cancer treatment.

METHODS

Nanosized poly(ester amine) polymer was synthesized and used as a gene carrier. An aerosol of poly(ester amine)/Akt1 siRNA complex was delivered into K-ras(LA1) and urethane-induced lung cancer models through a nose-only inhalation system. The effects of Akt1 siRNA on lung cancer progression and Akt-related signals were evaluated.

MEASUREMENTS AND MAIN RESULTS

The aerosol-delivered Akt1 siRNA suppressed lung tumor progression significantly through inhibiting Akt-related signals and cell cycle.

CONCLUSIONS

The use of poly(ester amine) serves as an effective carrier, and aerosol delivery of Akt1 siRNA may be a promising approach for lung cancer treatment and prevention.

摘要

理论依据

传统疗法在实现肺癌患者长期生存方面效率低下,这就需要开发新的治疗方案。气溶胶介导的基因递送技术的最新进展为肺癌的安全有效治疗提供了另一种可能性。

目的

证明无创气溶胶递送Akt1小干扰RNA(siRNA)作为肺癌治疗的有效且选择性方案的可行性,并强调其重要性。

方法

合成纳米级聚(酯胺)聚合物并用作基因载体。通过单鼻吸入系统将聚(酯胺)/Akt1 siRNA复合物气溶胶递送至K-ras(LA1)和聚氨酯诱导的肺癌模型中。评估Akt1 siRNA对肺癌进展和Akt相关信号的影响。

测量结果与主要结果

气溶胶递送的Akt1 siRNA通过抑制Akt相关信号和细胞周期,显著抑制了肺肿瘤进展。

结论

聚(酯胺)用作有效载体,气溶胶递送Akt1 siRNA可能是肺癌治疗和预防的一种有前景的方法。

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Sequential exposure to carbon nanotubes and bacteria enhances pulmonary inflammation and infectivity.依次暴露于碳纳米管和细菌会增强肺部炎症和感染性。
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