BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma

Abstract Background 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 dis...

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Main Authors: Li Ai, Zhijuan Liu, Ran Li, Ying Hu, Yongxia Li
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-025-03496-7
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author Li Ai
Zhijuan Liu
Ran Li
Ying Hu
Yongxia Li
author_facet Li Ai
Zhijuan Liu
Ran Li
Ying Hu
Yongxia Li
author_sort Li Ai
collection DOAJ
description Abstract Background 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. Methods 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). Results 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. Conclusions 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.
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spelling doaj-art-a848ea2aeab24562bfbcfa9b4fd2eb4c2025-08-20T02:10:32ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123111910.1186/s12951-025-03496-7BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung AdenocarcinomaLi Ai0Zhijuan Liu1Ran Li2Ying Hu3Yongxia Li4Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical UniversityDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical UniversityDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical UniversityDepartment of laboratory, The Second Affiliated Hospital of Kunming Medical UniversityDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Kunming Medical UniversityAbstract Background 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. Methods 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). Results 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. Conclusions 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.https://doi.org/10.1186/s12951-025-03496-7Lung adenocarcinomaMitophagyPRKN/AKT1 pathwayBPQDs@Lipo-YSAImmunogenic cell death (ICD)
spellingShingle Li Ai
Zhijuan Liu
Ran Li
Ying Hu
Yongxia Li
BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
Journal of Nanobiotechnology
Lung adenocarcinoma
Mitophagy
PRKN/AKT1 pathway
BPQDs@Lipo-YSA
Immunogenic cell death (ICD)
title BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
title_full BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
title_fullStr BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
title_full_unstemmed BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
title_short BPQDs@Lipo-YSA Nanoplatform Triggers Mitophagy via PRKN/AKT1 to Drive Immunogenic Cell Death in Lung Adenocarcinoma
title_sort bpqds lipo ysa nanoplatform triggers mitophagy via prkn akt1 to drive immunogenic cell death in lung adenocarcinoma
topic Lung adenocarcinoma
Mitophagy
PRKN/AKT1 pathway
BPQDs@Lipo-YSA
Immunogenic cell death (ICD)
url https://doi.org/10.1186/s12951-025-03496-7
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