pH-activated Heat Shock Protein Inhibition and Radical Generation Enhanced NIR Luminescence Imaging-guided Photothermal Tumour Ablation

Publication date: Available online 23 May 2019Source: International Journal of PharmaceuticsAuthor(s): Shuang Wang, Lin Li, Xiaohui Ning, Peidong Xue, Yuxin LiuAbstractPhotothermal 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.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research