Abstract
The overexpression of heat shock proteins (HSPs) in tumor cells can activate inherent defense mechanisms during hyperthermia-based treatments, inducing thermoresistance and thus diminishing the treatment efficacy. Here, we report a distinct "non-inhibitor involvement" strategy to address this issue through engineering a calcium-based nanocatalyst (G/A@CaCO3-PEG). The constructed nanocatalyst consists of calcium carbonate (CaCO3)-supported glucose oxidase (GOD) and 2D antimonene quantum dots (AQDs), with further surface modification by lipid bilayers and polyethylene glycol (PEG). The engineered G/A@CaCO3-PEG nanocatalyst features prolonged blood circulation, which is stable at neutral pH but rapidly degrades under mildly acidic tumor microenvironment, resulting in rapid release of drug cargo in the tumor microenvironment. The integrated GOD effectively catalyzes the depletion of glucose for reducing the supplies of adenosine triphosphate (ATP) and subsequent down-regulation of HSP expression. This effect then augments the therapeutic efficacy of photothermal hyperthermia induced by 2D AQDs upon irradiation with near-infrared light as assisted by reversing the cancer cells' thermoresistance. Consequently, synergistic antineoplastic effects can be achieved via low-temperature photothermal therapy. Systematic in vitro and in vivo evaluations have demonstrated that G/A@CaCO3-PEG nanocatalysts feature potent antitumor activity with a high tumor-inhibition rate (83.92%). This work thus paves an effective way for augmenting the hyperthermia-based tumor treatments via restriction of the ATP supply.