A multifunctional nanotheranostic for the intelligent MRI diagnosis and synergistic treatment of hypoxic tumor

Ruixue Song; Meng Zhang; Yanyan Liu; Zhaowen Cui; Hua Zhang; Zhongmin Tang; Xiaoyan Chen; Haihong Wu; Zhenwei Yao; Mingyuan He; Wenbo Bu

doi:10.1016/j.biomaterials.2018.05.018

A multifunctional nanotheranostic for the intelligent MRI diagnosis and synergistic treatment of hypoxic tumor

Biomaterials. 2018 Aug:175:123-133. doi: 10.1016/j.biomaterials.2018.05.018. Epub 2018 May 25.

Authors

Ruixue Song¹, Meng Zhang², Yanyan Liu¹, Zhaowen Cui², Hua Zhang³, Zhongmin Tang², Xiaoyan Chen¹, Haihong Wu⁴, Zhenwei Yao⁵, Mingyuan He¹, Wenbo Bu⁶

Affiliations

¹ Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, PR China.
² State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China.
³ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
⁴ Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, PR China. Electronic address: hhwu@chem.ecnu.edu.cn.
⁵ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, PR China. Electronic address: zwyao@fudan.edu.cn.
⁶ Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, PR China; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China. Electronic address: wbbu@chem.ecnu.edu.cn.

PMID: 29804000
DOI: 10.1016/j.biomaterials.2018.05.018

Abstract

Hypoxia, as an inevitable characteristic of solid tumors, has been regarded as a noticeably causative factor to therapeutic resistance and metastatic variants. Exploring novel theranostics to realize the accurate diagnosis of hypoxia and the simultaneous implementation of effective therapy is a promising prospect for the successful treatment of tumors. In the present study, we designed and synthesized a multifunctional rattle-structured nanotheranostic, with the inner core coated by hollow mesoporous silica for chemical drug Doxorubicin (DOX) storage and hypoxia-sensitive MnO₂ enrichment. In various acidic micro-environments caused by hypoxia, MnO₂ nanosheets could be degraded into manganese ions (Mn²⁺), which were chelated by the modified Tetraxetanum (DOTA) ligands for real-time T₁-magnetic resonance imaging (T₁-MRI), with on-demand DOX release to realize both normoxia and hypoxia-sensitive chemotherapy by overcoming hypoxia. Nanotheranostics integrating hypoxia-driven T₁-MRI with synergetic chemotherapy have tremendous potential in the intelligent diagnosis, personalized treatment and excellent prognosis of solid tumors in the future.

Keywords: Chemotherapy; Hypoxia tumor; Magnetic resonance imaging; Nanotechnology; Nanotheranostics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Cell Survival / drug effects
Contrast Media / chemistry
Doxorubicin / administration & dosage
Drug Carriers / chemistry*
Female
HeLa Cells
Heterocyclic Compounds, 1-Ring / chemistry
Humans
Magnetic Resonance Imaging
Manganese Compounds / chemistry
Mice
Mice, Nude
Nanoparticles / chemistry*
Neoplasms / diagnostic imaging*
Neoplasms / drug therapy*
Oxides / chemistry
Porosity
Silicon Dioxide / chemistry
Theranostic Nanomedicine
Tumor Hypoxia

Substances

Antineoplastic Agents
Contrast Media
Drug Carriers
Heterocyclic Compounds, 1-Ring
Manganese Compounds
Oxides
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Silicon Dioxide
Doxorubicin
manganese dioxide