Magnetic Targeting, Tumor Microenvironment-Responsive Intelligent Nanocatalysts for Enhanced Tumor Ablation.

Abstract

Therapeutic nanosystems which can be triggered by the distinctive tumor microenvironment possess great selectivity and safety to treat cancers via in situ transformation of nontoxic prodrugs into toxic therapeutic agents. Here, we constructed intelligent, magnetic targeting, and tumor microenvironment-responsive nanocatalysts that can acquire oxidation therapy of cancer via specific reaction at tumor site. The magnetic nanoparticle core of iron carbide-glucose oxidase (Fe5C2-GOD) achieved by physical absorption has a high enzyme payload, and the manganese dioxide (MnO2) nanoshell as an intelligent "gatekeeper" shields GOD from premature leaking until reaching tumor tissue. Fe5C2-GOD@MnO2 nanocatalysts maintained inactive in normal cells upon systemic administration. On the contrary, after endocytosis by tumor cells, tumor acidic microenvironment induced decomposition of MnO2 nanoshell into Mn2+ and O2, meanwhile releasing GOD. Mn2+ could serve as a magnetic resonance imaging (MRI) contrast agent for real-time monitoring treatment process. Then the generated O2 and released GOD in nanocatalysts could effectively exhaust glucose in tumor cells, simultaneously generating plenty of H2O2 which may accelerate the subsequent Fenton reaction catalyzed by the Fe5C2 magnetic core in mildly acidic tumor microenvironments. Finally, we demonstrated the tumor site-specific production of highly toxic hydroxyl radicals for enhanced anticancer therapeutic efficacy while minimizing systemic toxicity in mice.

• Authors: Lili Feng, Rui Xie, Chuanqing Wang, Shili Gai, Fei He, Dan Yang, Piaoping Yang, Jun Lin
• Journal: ACS nano (ACS Nano) Vol. 12 Issue 11 Pg. 11000-11012 (11 27 2018) ISSN: 1936-086X [Electronic] United States
• PMID: 30339353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carbon Compounds, Inorganic
• Iron Compounds
• Manganese Compounds
• Oxides
• iron carbide
• Glucose Oxidase
• manganese dioxide

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Carbon Compounds, Inorganic (chemistry, pharmacology)
• Catalysis
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Glucose Oxidase (chemistry, metabolism)
• HeLa Cells
• Humans
• Iron Compounds (chemistry, pharmacology)
• Magnetic Field Therapy
• Magnetic Resonance Imaging
• Manganese Compounds (chemistry, pharmacology)
• Mice
• Mice, Inbred Strains
• Nanoparticles (chemistry)
• Neoplasms, Experimental (drug therapy, pathology)
• Oxides (chemistry, pharmacology)
• Particle Size
• Surface Properties
• Tumor Microenvironment (drug effects)
• Uterine Cervical Neoplasms (drug therapy, pathology)