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

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; p. 209
• Main Authors: Du, Bin, Zheng, Mei, Ma, Huizhen, Huang, Jingshu, Jiao, Qingqing, Bai, Yimeng, Zhao, Mengmeng, Zhou, Jie
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.05.2022; BioMed Central; BMC
• Subjects: Apoptosis; Atheroembolism; Biotechnology; Cancer; Care and treatment; Catalysis; Catalytic oxidation; CD44 antigen; Cell membranes; Cell surface; Chemoprevention; Chemotherapy; Cholesterol; Cholesterol oxidase; Chondroitin; Chondroitin sulfate; Consumption; Diagnosis; Dosage and administration; Drug delivery systems; Drug resistance; Drug resistance in microorganisms; Drug Resistance, Multiple; Enzymes; Fluidity; Free radicals; Glycoproteins; Health aspects; Humans; Hydrogen Peroxide; Hydroxyl radicals; Lipid raft; Lipids; Membranes; Methods; Multidrug resistance; Multidrug resistant organisms; Nanoparticles; Neoplasms - drug therapy; P-Glycoprotein; Peroxidase; Prevention; Proteins; Reaction products; Risk factors; Tumor cells; Tumors; Ultrasonic imaging; China; Beijing China; Reverse drug resistance; Lipid raft; Fluidity; Cholesterol oxidase; Chondroitin sulfate; Cholesterol; Apoptosis
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01406-9

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 (NH -MIL-88B, MOF) through amide reaction, COD catalyzed the consumption of cholesterol, the reaction product H O was further produced by the MOF with its peroxidase-like activity to produce hydroxyl radicals (•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.