Shanghai Frontiers Science Center of Drug Target Identification and Delivery, School of School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
National Key Laboratory of Innovative Immunotherapy, Shanghai Jiao Tong University, Shanghai 200240, China.
ACS Appl Mater Interfaces. 2023 Jul 5;15(26):31273-31284. doi: 10.1021/acsami.3c05007. Epub 2023 Jun 24.
() 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 "si@GCLPP NPs," to treat -mutant non-small-cell lung cancer (NSCLC). The self-assembled si@GCLPP NPs are capable of maintaining structural integrity during nebulization, with preferential distribution within the tumor-bearing lung. Inhalable si@GCLPP NPs show not only significant tumor-targeting capability but also enhanced antitumor activity in an orthotopic mouse model of human -mutant NSCLC. The nebulized delivery of si@GCLPP NPs demonstrates potent knockdown of mutated 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 -mutant NSCLC and other respiratory diseases.
() 是肺癌中最常见的突变致癌基因。基因治疗作为一种有前途的癌症治疗方法正在兴起；然而，基因治疗的全身给药受到向肺部的有效传递和全身毒性的限制。在此，我们报告了一种非侵入性的雾化吸入纳米颗粒 (NP) 系统，称为“si@GCLPP NPs”，用于治疗 - 突变型非小细胞肺癌 (NSCLC)。自组装的 si@GCLPP NPs 在雾化过程中能够保持结构完整性，并且在带有肿瘤的肺部中具有优先分布。可吸入的 si@GCLPP NPs 不仅显示出显著的肿瘤靶向能力，而且在人 - 突变型 NSCLC 的原位小鼠模型中显示出增强的抗肿瘤活性。雾化递送 si@GCLPP NPs 可有效抑制荷瘤肺中的突变 ，而不会引起任何明显的不良反应，与全身递送方法相比，表现出更好的生物安全性。结果为治疗 - 突变型 NSCLC 和其他呼吸道疾病提供了一种有前途的吸入基因治疗方法。
