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Targeting Rab26 to Conquer Cisplatin-Resistant Lung Cancer with Self-Assembled DNA Nanomaterials

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机构: [1]Department of Thoracic Surgery, West China Hospital of Medicine, Sichuan University, Chengdu 610044, China. [2]Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. [3]Department of Pulmonary and Critical Care Medicine, The Second Hospital of Chongqing Medical University, Chongqing 400010, China. [4]Department of Respiratory Disease, General Hospital of Xinjiang Military Command, Urumqi 830000, China.
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Overcoming cisplatin-based drug resistance in lung cancer remains an enormous challenge in clinical tumor therapy worldwide. Recent studies have reported that some Rab GTPases are involved in multiple aspects of tumor progression, including invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. In particular, Rab26 is essential to vital processes such as vesicle-mediated secretion, cell growth, apoptosis, and autophagy. In this study, we developed a nanosystem based on programmed DNA self-assembly of Rab26 siRNA-loaded nanoparticles (siRNP). We demonstrated that siRNP could be effectively transfected into cisplatin-resistant A549 (A549/DDP) cells. These siRab26-carrying nanoparticles induced apoptosis and inhibited the disruption of autophagy. The combination therapy of siRab26 knockdown with cisplatin could improve the antitumor therapy compared with a single one in vitro. In nude mice, siRNP enhanced the chemosensitivity of cisplatin-resistant cells and inhibited tumor xenograft development. These outcomes suggest that siRNP is an effective platform for lung cancer therapy in cases exhibiting drug resistance.

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出版当年[2023]版:
大类 | 2 区 化学
小类 | 1 区 有机化学 1 区 高分子科学 2 区 生化与分子生物学
最新[2023]版:
大类 | 2 区 化学
小类 | 1 区 有机化学 1 区 高分子科学 2 区 生化与分子生物学
第一作者:
第一作者机构: [1]Department of Thoracic Surgery, West China Hospital of Medicine, Sichuan University, Chengdu 610044, China. [2]Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
通讯作者:
通讯机构: [1]Department of Thoracic Surgery, West China Hospital of Medicine, Sichuan University, Chengdu 610044, China. [2]Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. [*1]Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China [*2]Department of Thoracic Surgery, West China Hospital of Medicine, Sichuan University, Chengdu 610044, China
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