在世界肿瘤临床治疗中，克服肺癌铂类药物抗性仍然是一个巨大的挑战。最近的研究报道称，一些Rab GTP酶参与了肿瘤进展的多个方面，包括侵袭、迁移、代谢、自噬、外泌体分泌和药物抗性。特别地，Rab26对于囊泡介导的分泌、细胞生长、凋亡和自噬等重要过程至关重要。在本研究中，我们开发了一种基于编程DNA自组装的Rab26 siRNA负载纳米粒子（siRNP）纳米系统。我们证明了siRNP可以有效地转染铂类耐药A549（A549/DDP）细胞。这些携带siRab26的纳米粒子诱导细胞凋亡并抑制自噬的破坏。与单一疗法相比，siRab26抑制与铂类药物的联合疗法可以改善体外的抗肿瘤疗法。在裸鼠中，siRNP增强了铂类耐药细胞的化疗敏感性并抑制了肿瘤异种移植的发展。这些结果表明，对于表现出药物抗性的肺癌疗法，siRNP是一种有效的平台。

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.