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.

Combined Effects of Plant Sterols with Low Ratio of n-6/n-3 Polyunsaturated Fatty Acids against Atherosclerosis in ApoE-/- Mice.

The effects of low ratio of n-6/n-3 polyunsaturated fatty acids (PUFA) have been clarified against atherosclerosis. Increasing evidence indicated that plant sterols (PS) have a significant cholesterol-lowering effect. This study explored the effects of PS combined with n-6/n-3 (2:1) PUFA on atherosclerosis and investigated the possible mechanism. In ApoE-/- mice, the milk fat in high fat diets was replaced with n-6/n-3 (2:1) PUFA alone or supplemented with 6% PS for 16 weeks. Results demonstrated that PS combined with PUFA exerted commentary and synergistic effects on ameliorating atherosclerosis, improving lipid metabolism and lipid deposition in liver, and alleviating inflammatory response. These changes were accompanied with decreased serum TC, TG, LDL-C and increased fecal cholesterol efflux, as well as the lower inflammatory cytokine CRP, IL-6, TNF-α. It is suggested that the underlying mechanism of PS combined with n-6/n-3 (2:1) PUFA promoting the fecal cholesterol efflux may be mediated by liver X receptor α/ATP-binding cassette transporter A1 pathway.