Biodegradable Manganese-Doped Calcium Phosphate Nanotheranostics for Traceable Cascade Reaction-Enhanced Anti-Tumor Therapy.

Abstract

Glucose oxidase (GOx) has been recognized as a "star" enzyme catalyst involved in cancer treatment in the past few years. Herein, GOx is mineralized with manganese-doped calcium phosphate (MnCaP) to form spherical nanoparticles (GOx-MnCaP NPs) by an in situ biomimetic mineralization method, followed by the loading of doxorubicin (DOX) to construct a biodegradable, biocompatible, and tumor acidity-responsive nanotheranostics for magnetic resonance imaging (MRI) and cascade reaction-enhanced cooperative cancer treatment. The GOx-driven oxidation reaction can effectively eliminate intratumoral glucose for starvation therapy, and the elevated H2O2 is then converted into highly toxic hydroxyl radicals via a Mn2+-mediated Fenton-like reaction for chemodynamic therapy (CDT). Moreover, the acidity amplification due to the gluconic acid generation will in turn accelerate the degradation of the nanoplatform and promote the Mn2+-H2O2 reaction for enhanced CDT. Meanwhile, the released Mn2+ ions can be used for MRI to monitor the treatment process. After carrying the anticancer drug, the DOX-loaded GOx-MnCaP can integrate starvation therapy, Mn2+-mediated CDT, and DOX-induced chemotherapy together, which showed greatly improved therapeutic efficacy than each monotherapy. Such an orchestrated cooperative cancer therapy demonstrated high-efficiency tumor suppression on 4T1 tumor-bearing mice with minimal side effects. Our findings suggested that the DOX-loaded GOx-MnCaP nanotheranostics with excellent biodegradability and biocompatibility hold clinical translation potential for cancer management.

• Authors: Lian-Hua Fu, Yan-Ru Hu, Chao Qi, Ting He, Shanshan Jiang, Chao Jiang, Jin He, Junle Qu, Jing Lin, Peng Huang
• Journal: ACS nano (ACS Nano) Vol. 13 Issue 12 Pg. 13985-13994 (12 24 2019) ISSN: 1936-086X [Electronic] United States
• PMID: 31833366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biocompatible Materials
• Calcium Phosphates
• Manganese
• Doxorubicin
• calcium phosphate
• Glucose Oxidase

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Biocompatible Materials (chemistry)
• Calcium Phosphates (chemistry)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Doxorubicin (therapeutic use)
• Female
• Glucose Oxidase (metabolism)
• Humans
• Magnetic Resonance Imaging
• Manganese (chemistry)
• Mice, Inbred BALB C
• Nanoparticles (chemistry, ultrastructure)
• Spectrophotometry, Ultraviolet
• Theranostic Nanomedicine