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 shock proteins (HSPs) is the major factor that seriously hinders further application of PTT, as it can lead to tumor inflammation, invasion, and even recurrence. Therefore, new strategies to inhibit HSPs expression are essential to improve the antitumor efficacy of PTT. Here, we prepared a novel nanoparticle inhibitor by synthesizing molecularly imprinted polymers with a high imprinting factor (3.1) on the Prussian Blue surface (PB@MIP) for combined tumor starvation and photothermal therapy. Owing to using hexokinase (HK) epitopes as the template, the imprinted polymers could inhibit the catalytic activity of HK to interfere with glucose metabolism by specifically recognizing its active sites and then achieve starvation therapy by restricting ATP supply. Meanwhile, MIP-mediated starvation downregulated the ATP-dependent expression of HSPs and then sensitized tumors to hyperthermia, ultimately improving the therapeutic effect of PTT. As the inhibitory effect of PB@MIP on HK activity, more than 99% of the mice tumors were eliminated by starvation therapy and enhanced PTT.

H2O2 self-supplying degradable epitope imprinted polymers for targeted fluorescence imaging and chemodynamic therapy.

Chemodynamic therapy (CDT), the ability to transform H2O2 into a highly toxic hydroxyl radical (˙OH) through a Fenton or Fenton like reaction to kill cancer cells, enables selective tumor therapy. However, the effect is seriously limited by the insufficiency of endogenous H2O2 in cancer cells. Additionally, the specific recognition of epitope imprinting plays an important role in targeting cancer cell markers. In this work, we prepared H2O2 self-supplying degradable epitope molecularly imprinted polymers (MIP) for effective CDT, employing fluorescent calcium peroxide (FCaO2) as an imaging probe and a source of H2O2, the exposed peptide in the CD47 extracellular region as the template, copper acrylate as one of the functional monomers and N,N'-bisacrylylcystamine (BAC) as a cross-linker. MIP with recognition sites can specifically target CD47-positive cancer cells to achieve fluorescence imaging. Under the reduction of glutathione (GSH), the MIP were degraded and the exposed FCaO2 reacted with water to continuously produce H2O2 in the slightly acidic environment in cancer cells. The self-supplied H2O2 produced ˙OH through a Fenton like catalytic reaction mediated by copper ions in the MIP framework, inducing cancer cell apoptosis. Therefore, the MIP nano-platform, which was capable of specific recognition of the cancer cell marker, H2O2 self-supply and controlled treatment, was successfully used for targeted CDT.