Nanozyme-natural enzymes cascade catalyze cholesterol consumption and reverse cancer multidrug resistance

Multidrug resistance is still a major obstacle to cancer treatment. The most studies are to inhibit the activity of the drug transporter P-glycoprotein (P-gp), but the effect is not ideal. Herein, a nanosystem was built based on cascade catalytic consumption of cholesterol. Cholesterol oxidase (natural enzyme, COD) was immobilized on the carrier (NH2-MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H2O2 was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (center dot OH) with killing effect. Due to the high expression of CD44 receptor on the surface of tumor cells, we encapsulated chondroitin sulfate gel shell (CS-shell) with CD44 targeting and apoptosis promoting effect on the surface of DOX@MOF-COD nanoparticles, which can accurately and efficiently deliver the drugs to the tumor site and improve the effect of reversing drug resistance. Taking drug-resistant cell membrane as breakthrough, this paper will provide a new idea for reversing multidrug resistance of tumor.

Automated summary

This study established a new nanosystem to reverse multidrug resistance by using cascade catalytic consumption of cholesterol. By encapsulating CD44 targeting chondroitin sulfate gel shell, drugs can be accurately and efficiently delivered to the tumor site, improving the effect of reversing drug resistance.