pH-activated heat shock protein inhibition and radical generation enhanced NIR luminescence imaging-guided...

Photothermal therapy had great potential in being a new approach of tumour ablation due to their high selectivity and low side effect. However, the shallow penetration depth of near-infrared (NIR) irradiation resulted in the limited curative effect. Herein, a novel nanomedicine was developed based on the indocyanine green-loaded vanadium oxide nanocomposites (VO₂-ICG) for pH-activated NIR luminescence imaging-guided enhanced photothermal tumour ablation. In acidic tumour microenvironment, the VO₂ NPs were decomposed and released VO²⁺, which could not only inhibit the function of 60 kDa heat shock protein (HSP60), but also generate hydroxyl radical (OH) by catalysing intratumoral H₂O₂. Furthermore, the ICG was also released in the decomposition process of VO₂ NPs, allowing the pH-activated NIR luminescence imaging and photothermal therapy. The inhibition of HSP60 down-regulated the heat tolerance of cells and the generation of OH up-regulated the intracellular oxidative stress, which enhanced the photothermal therapeutic efficiency. Our work demonstrated a promised method to enhance photothermal therapeutic effect, highlighting the importance of HSP inhibition and OH generation in promoting cell apoptosis under mild hyperthermia.