Unleashing the potential: NIR-II imaging-guided tumor therapy with enhanced HPTT/starvation cycle

Establishing a phototheranostic platform constructed by the second near-infrared (NIR-II) region has proved a revolutionary and promising strategy for cancer treatment. However, the antitumor effectiveness is severely limited by the monotonicity of the NIR-photothermal therapy (HPTT) modality and tumor thermotolerance caused by the production of heat shock proteins (HSPs). Here, a minimalistic approach is used to construct an organic nanoplatform (IFT@PEG-GOX NPs) with the reciprocal cyclic promotion of hypothermia and starvation treatments for NIR-II imaging-guided tumor therapy. After the enhanced permeability and retention (EPR) effect causes IFT@PEG-GOX NPs to accumulate in tumors, glucose oxidase (GOx)-mediated tumor starvation may obstruct the production of adenosine triphosphate (ATP) and downregulation heat shock proteins (HSPs), thereby reducing the thermotolerance of cells. After that, sensitized HPTT was activated and GOx's catalytic activity was increased by NIR laser irradiation. Then, there would be a subsequent, intensified inhibition of HSP along with an additional amplification of the GOx-mediated tumor starvation. As a consequence, the HPTT/Starvation therapy (ST) bidirectional cycle method is initiated, leading to a bidirectional cyclic enhancing impact of HPTT and ST and significantly better tumor suppression.