Facile Deposition of Manganese Dioxide to Albumin-Bound Paclitaxel Nanoparticles for Modulation of Hypoxic Tumor Microenvironment To Improve Chemoradiation Therapy

Lingtong Meng; Yali Cheng; Shaoju Gan; Zhicheng Zhang; Xiaoning Tong; Lei Xu; Xing Jiang; Yishen Zhu; Jinhui Wu; Ahu Yuan; Yiqiao Hu

doi:10.1021/acs.molpharmaceut.7b00808

Facile Deposition of Manganese Dioxide to Albumin-Bound Paclitaxel Nanoparticles for Modulation of Hypoxic Tumor Microenvironment To Improve Chemoradiation Therapy

Mol Pharm. 2018 Feb 5;15(2):447-457. doi: 10.1021/acs.molpharmaceut.7b00808. Epub 2018 Jan 8.

Authors

Lingtong Meng¹, Yali Cheng¹, Shaoju Gan¹, Zhicheng Zhang¹, Xiaoning Tong¹, Lei Xu^{1

2}, Xing Jiang¹, Yishen Zhu², Jinhui Wu^{1

3

4}, Ahu Yuan^{1

3

4}, Yiqiao Hu^{1

3

4}

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University , Nanjing 210093, China.
² College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University , Nanjing 211800, China.
³ Jiangsu Key Laboratory for Nano Technology, Nanjing University , Nanjing 210093, China.
⁴ Institute of Drug R&D, Medical School of Nanjing University , Nanjing 210093, China.

PMID: 29261319
DOI: 10.1021/acs.molpharmaceut.7b00808

Abstract

Tumor microenvironment with hypoxia and excess hydrogen peroxide (H₂O₂) tremendously limits the effect of chemoradiation therapy of colorectal cancer. For the first time, we developed a facile method to deposit manganese dioxide (MnO₂) on the surface of albumin bound paclitaxel nanoparticles (ANPs-PTX) to obtain MnO₂-functioned ANPs-PTX (MANPs-PTX). In the tumor microenvironment, MANPs-PTX could consume excess hydrogen peroxide (H₂O₂) to produce abundant oxygen for tumor oxygenation and improve chemoradiation therapy. Meanwhile, the released Mn²⁺ from MANPs-PTX had excellent T₁ magnetic resonance imaging (MRI) performances for tumor detection. Notably, the obtained MANPs-PTX would be a promising theranostic agent and have potential clinical application prospects.

Keywords: albumin-bound paclitaxel nanoparticles; chemoradiation therapy; magnetic resonance imaging; manganese dioxide; oxygenation; tumor microenvironment.

Publication types

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

MeSH terms

Albumin-Bound Paclitaxel / administration & dosage*
Albumin-Bound Paclitaxel / chemistry
Animals
Antineoplastic Agents / administration & dosage*
Antineoplastic Agents / chemistry
Cell Hypoxia / drug effects
Cell Line, Tumor / transplantation
Chemoradiotherapy / methods
Colorectal Neoplasms / diagnostic imaging
Colorectal Neoplasms / therapy*
Disease Models, Animal
Drug Compounding / methods*
Humans
Hydrogen Peroxide / metabolism
Male
Manganese Compounds / chemistry*
Mice
Mice, Inbred BALB C
Nanoparticles / administration & dosage
Nanoparticles / chemistry
Oxides / chemistry*
Treatment Outcome
Tumor Burden / drug effects
Tumor Burden / radiation effects
Tumor Microenvironment / drug effects

Substances

Albumin-Bound Paclitaxel
Antineoplastic Agents
Manganese Compounds
Oxides
Hydrogen Peroxide
manganese dioxide