克拉斯
癌症研究
肺癌
全身给药
基因敲除
癌症
癌基因
突变体
医学
材料科学
生物
细胞培养
肿瘤科
基因
体内
内科学
结直肠癌
细胞周期
生物化学
遗传学
生物技术
作者
Guolin Zhao,William Ho,Jinxian Chu,X. Xiong,Bin Hu,Kofi Oti Boakye‐Yiadom,Xiaoyang Xu,Xue‐Qing Zhang
标识
DOI:10.1021/acsami.3c05007
摘要
Kirsten rat sarcoma (KRAS) is the most commonly mutated oncogene in lung cancers. Gene therapy is emerging as a promising cancer treatment modality; however, the systemic administration of gene therapy has been limited by inefficient delivery to the lungs and systemic toxicity. Herein, we report a noninvasive aerosol inhalation nanoparticle (NP) system, termed "siKRAS@GCLPP NPs," to treat KRAS-mutant non-small-cell lung cancer (NSCLC). The self-assembled siKRAS@GCLPP NPs are capable of maintaining structural integrity during nebulization, with preferential distribution within the tumor-bearing lung. Inhalable siKRAS@GCLPP NPs show not only significant tumor-targeting capability but also enhanced antitumor activity in an orthotopic mouse model of human KRAS-mutant NSCLC. The nebulized delivery of siKRAS@GCLPP NPs demonstrates potent knockdown of mutated KRAS in tumor-bearing lungs without causing any observable adverse effects, exhibiting a better biosafety profile than the systemic delivery approach. The results present a promising inhaled gene therapy approach for the treatment of KRAS-mutant NSCLC and other respiratory diseases.
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