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. Graphical Abstract