A self-supplied O2 versatile nanoplatform for GOx-mediated synergistic starvation and hypothermal photothermal therapy

Abstract

Hypothermal photothermal therapy, as a non-invasive therapy method, is becoming ever more prevalent. However, due to cellular heat resistance from the generation of heat shock proteins (HSPs) and the monotonicity of therapeutic modality, the antitumor efficacy is severely restricted. Herein, a self-supplied O2 multifunctional nanoplatform mediated by glucose oxidase (GOx) is developed, which may combine starvation therapy (ST) and hypothermal photothermal therapy (HPTT) for tumor therapy. The obtained nanoplatform, UM@ICG@GOX@HA (UMIGH), was assembled by the UIO-66 core, MnO2, indocyanine green (ICG) and hyaluronic acid (HA). GOx was introduced to decrease the ATP level thus alleviating the HSPs-mediated heat tolerance, while the loaded MnO2 could decompose intratumoral H2O2 into O2, which enhanced the effect of HPTT and ST. Due to the coated HA, UMIGH could target the high expressed CD44 in CT26 tumor cells. The active targeting and NPs-associated passive targeting promoted the uptake of nanoparticles. Furthermore, ICG encapsulated in UMIGH NPs could also accurately image tumors. This synergistic treatment strategy of HPTT and ST exhibited an excellent anti-proliferation effect on colon cancer cells in vitro and mouse xenograft model in vivo, which might bring an informatic strategy for future investigations.

Keywords

• Metal–organic frameworks
• Hypothermal photothermal therapy
• Hypoxia
• Starvation therapy
• Thermoresistance