Implantable Nanofiber Membranes with Synergistic Photothermal and Autophagy Inhibition Effects for Enhanced Tumor Therapy Efficacy
Jiaxiang Mu , Zhaoxu Meng , Xinran Liu , Ping Guan , He Lian
Advanced Fiber Materials ›› 2023, Vol. 5 ›› Issue (5) : 1810 -1825.
Implantable Nanofiber Membranes with Synergistic Photothermal and Autophagy Inhibition Effects for Enhanced Tumor Therapy Efficacy
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.
Scientific Research Projects of Liaoning Provincial Department of Education(LJKMZ20221354)
Cultivation Fund Project of National Natural Science Foundation of Shenyang Pharmaceutical University(PYJJ2021101)
Career Development Support Program for Young and Middle-aged Teachers of Shenyang Pharmaceutical University(ZQN202208)
Natural Science Foundation of Liaoning Province(2023-MS-198)
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