Oncolytic Nanoreactors Producing Hydrogen Peroxide for Oxidative Cancer Therapy

• Published in: Nano letters 2020-01, Vol.20 (1), p.526-533
• Main Authors: Jo, Seong-Min, Wurm, Frederik R, Landfester, Katharina
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Caco-2 Cells; Glucose Oxidase - chemistry; Glucose Oxidase - pharmacokinetics; Glucose Oxidase - pharmacology; HeLa Cells; Humans; Hydrogen Peroxide - pharmacokinetics; Hydrogen Peroxide - pharmacology; MCF-7 Cells; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Oxidation-Reduction - drug effects
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.9b04263

In situ generation of anticancer agents at the place of the disease is a new paradigm for cancer therapy. The production of highly potent drugs by nanoreactors through a facile synthesis pathway is demanded. We report an oncolytic nanoreactor platform loaded with the enzyme glucose oxidase (GOX) to produce hydrogen peroxide. For the first time, we realized a core–shell structure with encapsulated GOX under mild synthetic conditions, which ensured high remaining activity of GOX inside of the nanoreactor. Moreover, the nanoreactor protected the loaded GOX from proteolysis and contributed to increased thermal stability of the enzyme. The nanoreactors were effectively taken up into different cancer cells, in which they produced hydrogen peroxide by consuming intracellular glucose and oxygen, thereby leading to effective death of the cancer cells. In summary, our robust nanoreactors are a promising platform for effective anticancer therapy and sustained enzyme utilization.