Tumor-Specific Nanomedicine via Sequential Catalytic Reactions for Accurate Tumor Therapy
Catalytic medicine based on various catalysts has attracted increasing interest for tumor treatment. However, the direct application of conventional catalysts may cause serious side effects to healthy tissue and low therapeutic efficiency to tumor tissue, due to the its weak selectivity to tumor microenvironment (TME). Herein, a tumor-targeting and TME-responsive nanocage containing ferroferric oxide nanoparticles (Fe3O4 NPs) and glucose oxidase (GOD) was developed to perform hyaluronidase (HAase) and glutathione (GSH) triggered chain catalytic reactions in tumor tissue, which takes advantage of unique biological molecules in tumor and several therapeutic agents to adjust the local microenvironments for satisfactory and accurate tumor therapy. The reactions started from consumption of intratumoral glucose to inhibit tumor growth, which simultaneously produce hydrogen peroxide (H2O2) to make up the deficiency of H2O2 in original tumor microenvironment, resulting in generation of high amount of hydroxyl radicals under the catalysis of Fe3O4 NPs to further eliminate tumor tissue. The tumor selective catalytic medicine preformed by our nanocomposite guaranteed both therapeutic efficiency and accuracy avoiding potential risks to healthy tissue, leading an fourfold cytotoxicity against tumor cells compared with normal cells after 48 h incubation. In vivo data from mouse models provided further evidence about its therapeutic efficacy that the tumor can be completely inhibited after two weeks of the synergistic therapy, which indicated the promising candidate of our nanocomposite for tumor treatment.