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Implantable Nanofiber Membranes with Synergistic Photothermal and Autophagy Inhibition Effects for Enhanced Tumor Therapy Efficacy

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Abstract

Photothermal therapy (PTT) has been proposed as an advanced patient-centered strategy for tumor treatment. Nevertheless, the uncertain safety of conventional photothermal conversion agents and the presence of intracellular self-protective autophagy mechanisms pose obstacles to the clinical application and efficacy of PTT. As we are deeply aware of the seriousness of these problems, we herein proposed an efficacy-enhancing strategy based on an implantable membrane platform (PPG@PB-HCQ) constructed from poly (lactic acid) (PLA), poly (ɛ-caprolactone) (PCL) and gelatin (Gel) electrospun nanofibers (PPG) and loaded with the biodegradable high-efficiency photothermal conversion agent Prussian blue (PB) and the autophagy inhibitor hydroxychloroquine sulfate (HCQ). Cellular experiments confirmed that the PPG@PB-HCQ nanofiber membrane exhibited a significantly stronger tumor cell-killing effect compared with the PTT alone. This enhancement features by of blocking the fusion of autophagosomes with lysosomes. The intracellular overexpression of the proteins microtubule-associated protein 1 light chain 3 (LC3)-II and p62 and the low expression of the proteins LC3-I and Rab7 (members of the RAS oncogene family) further demonstrated autophagic flux blockade. Importantly, the potent antitumor effect of the PPG@PB-HCQ therapeutic platform in B16 tumor-bearing model mice verified the efficacy-enhancing strategy of synergistic PTT and protective autophagy blockade. The present study provides a promising strategy for solving the difficulties of tumor treatment, as well as a new perspective for designing novel treatment platforms.

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Acknowledgements

This work was supported by the Scientific Research Projects of Liaoning Provincial Department of Education (Grant No: LJKMZ20221354), Natural Science Foundation of Liaoning Province (Grant No: 2023-MS-198), Cultivation Fund Project of National Natural Science Foundation (Grant No: PYJJ2021101) and Career Development Support Program for Young and Middle-aged Teachers (Grant No: ZQN202208) of Shenyang Pharmaceutical University. The authors would like to thank the Shiyanjia lab (www.Shiyanjia.com) for the SEM, DSC and XRD tests.

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  1. Jiaxiang Mu and Zhaoxu Meng equally contributed to this work.

Authors and Affiliations

  1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Jiaxiang Mu, Xinran Liu & Ping Guan

  2. Department of Biomedical Engineering, School of Medical Instrumentation, Shenyang Pharmaceutical University, Shenyang, 110016, China

    Zhaoxu Meng & He Lian

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  1. Jiaxiang Mu
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Correspondence to He Lian.

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Mu, J., Meng, Z., Liu, X. et al. Implantable Nanofiber Membranes with Synergistic Photothermal and Autophagy Inhibition Effects for Enhanced Tumor Therapy Efficacy. Adv. Fiber Mater. 5, 1810–1825 (2023). https://doi.org/10.1007/s42765-023-00311-6

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