Ai Li, Liu Zhijuan, Li Ran, Hu Ying, Li Yongxia
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical University, No 374 Dianmian Road, Kunming, 650101, Yunnan, China.
Department of laboratory, The Second Affiliated Hospital of Kunming Medical University, No 374 Dianmian Road, Kunming, 650101, Yunnan, China.
J Nanobiotechnology. 2025 Jun 16;23(1):446. doi: 10.1186/s12951-025-03496-7.
Lung adenocarcinoma, the most common type of non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths globally due to its high incidence and treatment difficulty. Despite recent advancements in treatment methods, the prognosis for patients with advanced disease remains poor. Studies have shown that targeting mitophagy, the selective clearance of damaged mitochondria, can influence the sensitivity of cancer cells to treatment.
In this study, we designed and synthesized BPQDs@Lipo-YSA, a novel nanomaterial, aimed at specifically inducing mitophagy in lung adenocarcinoma cells. The nanomaterial was characterized using techniques such as transmission electron microscopy (TEM) and dynamic light scattering (DLS). The ability of BPQDs@Lipo-YSA to induce mitophagy was evaluated using Western blot, immunofluorescence, and flow cytometry. Additionally, in vitro and in vivo experiments were conducted to investigate the impact of BPQDs@Lipo-YSA on lung adenocarcinoma cells through the induction of immunogenic cell death (ICD).
Experimental results showed that BPQDs@Lipo-YSA effectively induced mitophagy in lung adenocarcinoma cells by activating the PRKN/AKT1 pathway. More importantly, this induction of mitophagy significantly enhanced the cytotoxic effect on lung adenocarcinoma cells. In animal models, BPQDs@Lipo-YSA, by inducing ICD, markedly inhibited tumor growth and extended survival.
This study reveals the potential value of BPQDs@Lipo-YSA in lung adenocarcinoma treatment through the induction of mitophagy and ICD. This finding provides theoretical and technical support for the development of new therapeutic strategies for lung adenocarcinoma.
肺腺癌是最常见的非小细胞肺癌（NSCLC）类型，因其高发病率和治疗难度，是全球癌症相关死亡的主要原因。尽管治疗方法最近有所进展，但晚期疾病患者的预后仍然很差。研究表明，靶向线粒体自噬（受损线粒体的选择性清除）可影响癌细胞对治疗的敏感性。
在本研究中，我们设计并合成了一种新型纳米材料BPQDs@Lipo-YSA，旨在特异性诱导肺腺癌细胞中的线粒体自噬。使用透射电子显微镜（TEM）和动态光散射（DLS）等技术对该纳米材料进行了表征。使用蛋白质免疫印迹法、免疫荧光法和流式细胞术评估了BPQDs@Lipo-YSA诱导线粒体自噬的能力。此外，还进行了体外和体内实验，以研究BPQDs@Lipo-YSA通过诱导免疫原性细胞死亡（ICD）对肺腺癌细胞的影响。
实验结果表明，BPQDs@Lipo-YSA通过激活PRKN/AKT1途径有效诱导肺腺癌细胞中的线粒体自噬。更重要的是，这种线粒体自噬的诱导显著增强了对肺腺癌细胞的细胞毒性作用。在动物模型中，BPQDs@Lipo-YSA通过诱导ICD，显著抑制肿瘤生长并延长生存期。
本研究揭示了BPQDs@Lipo-YSA通过诱导线粒体自噬和ICD在肺腺癌治疗中的潜在价值。这一发现为肺腺癌新治疗策略的开发提供了理论和技术支持。
