Evidence map›Paper›PMID 41993628›Full record

ArticleTheranostics2026

Synergistic nanomedicine overcomes hypoxia-driven DNA repair to potentiate radiotherapy for lung adenocarcinoma.

Zhichang Liu, Yue Qiu, Jie Chen, Jue Li, Cheng Zhuang, Qiyi Feng, Jinxing Huang, Chunxiu Xiao, Xiuli Zheng, Kui Luo and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Zhichang LiuLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yue QiuLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jie ChenLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jue LiLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Cheng ZhuangLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Qiyi FengLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jinxing HuangLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Chunxiu XiaoLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Xiuli ZhengLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Kui LuoLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.
Kai XiaoLaboratory of Precision Therapeutics, Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institution of Radiology and Medical Imaging, Huaxi MR Research Center (HMRRC), Department of Radiology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleRadiotherapy (RT) remains a mainstay for inoperable lung adenocarcinoma (LUAD), while its efficacy is frequently compromised by hypoxia-driven radioresistance. Hypoxia stabilizes hypoxia-inducible factor-1α (HIF-1α), which triggers pro-repair DNA damage response (DDR) programs. This process intensifies replication stress and ultimately enhances tumor dependence on ataxia-telangiectasia and Rad3-related (ATR)-dependent checkpoint signaling for survival. Coordinated suppression of these adaptive programs may overcome hypoxia-driven tolerance to RT and improve therapeutic responses.

methodsThe clinical relevance of HIF-1α and ATR signaling in LUAD was established through integrative bioinformatic analyses of a patient cohort. A redox-responsive polymeric nanoplatform incorporating gadolinium (Gd³⁺) and pyropheophorbide a (Ppa) was constructed to enable X-ray-activated radiodynamic therapy (RDT) and co-deliver HIF-1α siRNA with AZD6738, an ATR inhibitor. Therapeutic efficacy, radiosensitization, and mechanisms were studied

resultsBioinformatic analyses support the rationale for simultaneously targeting hypoxia-adaptive programs and checkpoint-mediated DDR. The nanomedicine achieves efficient co-delivery of HIF-1α siRNA and AZD6738, suppressing hypoxia-driven adaptation and impairing ATR-dependent checkpoint protection. In addition, Gd³⁺ promotes X-ray energy deposition to activate Ppa, amplifying radiodynamic reactive oxygen species (ROS) generation. These complementary biological and physicochemical actions synergistically enhance tumor cell killing and markedly improve radiosensitivity

conclusionsThis study establishes a synergistic nanotherapeutic strategy to concurrently disrupt the HIF-1α/ATR axis and augment radiodynamic ROS production. By integrating biological pathway inhibition with damage amplification, our strategy effectively overcomes hypoxia-mediated radioresistance, offering a promising and translatable paradigm for enhancing RT outcomes in LUAD.

Indexed as

Adenocarcinoma of LungDNA RepairLung NeoplasmsNanomedicineAnimalsAtaxia Telangiectasia Mutated ProteinsCell Line, TumorGadoliniumHumansHypoxia-Inducible Factor 1, alpha SubunitMiceRadiation-Sensitizing AgentsRNA, Small InterferingXenograft Model Antitumor AssaysAtaxia Telangiectasia Mutated ProteinsGadoliniumHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitRadiation-Sensitizing AgentsRNA, Small Interferingcombination therapyDNA damage repairhypoxialung adenocarcinomananomedicineradiosensitivity

Identifiers

PMID41993628
PMCPMC13080800

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.