A Novel Hexokinases Inhibitor Based on Molecularly Imprinted Polymer for Combined Starvation and Enhanced Photothermal Therapy of Malignant Tumors

The heat tolerance of tumor cells induced by heat shockproteins(HSPs) is the major factor that seriously hinders further applicationof PTT, as it can lead to tumor inflammation, invasion, and even recurrence.Therefore, new strategies to inhibit HSPs expression are essentialto improve the antitumor efficacy of PTT. Here, we prepared a novelnanoparticle inhibitor by synthesizing molecularly imprinted polymerswith a high imprinting factor (3.1) on the Prussian Blue surface (PB@MIP)for combined tumor starvation and photothermal therapy. Owing to usinghexokinase (HK) epitopes as the template, the imprinted polymers couldinhibit the catalytic activity of HK to interfere with glucose metabolismby specifically recognizing its active sites and then achieve starvationtherapy by restricting ATP supply. Meanwhile, MIP-mediated starvationdownregulated the ATP-dependent expression of HSPs and then sensitizedtumors to hyperthermia, ultimately improving the therapeutic effectof PTT. As the inhibitory effect of PB@MIP on HK activity, more than99% of the mice tumors were eliminated by starvation therapy and enhancedPTT.

Automated summary

A novel nanoparticle inhibitor, PB@MIP, was prepared by synthesizing molecularly imprinted polymers on the Prussian Blue surface. It achieved combined tumor starvation and photothermal therapy by inhibiting the catalytic activity of hexokinase (HK) and downregulating the ATP-dependent expression of heat shock proteins (HSPs). This improved the therapeutic effect of photothermal therapy by sensitizing tumors to hyperthermia.