Hydrangea-structured tumor microenvironment responsive degradable nanoplatform for hypoxic tumor multimodal imaging and therapy

Qianyun Tang; Zijin Cheng; Nan Yang; Qinzhe Li; Peng Wang; Dapeng Chen; Wenjun Wang; Xuejiao Song; Xiaochen Dong

doi:10.1016/j.biomaterials.2019.03.005

Hydrangea-structured tumor microenvironment responsive degradable nanoplatform for hypoxic tumor multimodal imaging and therapy

Biomaterials. 2019 Jun:205:1-10. doi: 10.1016/j.biomaterials.2019.03.005. Epub 2019 Mar 15.

Authors

Qianyun Tang¹, Zijin Cheng¹, Nan Yang¹, Qinzhe Li¹, Peng Wang¹, Dapeng Chen¹, Wenjun Wang², Xuejiao Song³, Xiaochen Dong⁴

Affiliations

¹ Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, China.
² School of Physical Science and Information Technology, Liaocheng University, Liaocheng, 252059, China.
³ Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, China. Electronic address: songxuejiao8888@163.com.
⁴ Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, China. Electronic address: iamxcdong@njtech.edu.cn.

PMID: 30889497
DOI: 10.1016/j.biomaterials.2019.03.005

Abstract

Developing new strategies to alleviate tumor hypoxia and enhance the therapeutic efficacy towards solid tumors is of great significance to tumor therapy. Herein, to overcome tumor hypoxia, specifically designed aza-BODIPY photosensitizer is co-loaded with anti-cancer drug (doxorubicin, DOX) onto the hydrangea-structured MnO₂ nanoparticles, and a tumor microenvironment (TME) responsive degradable nanoplatform (MDSP NP) is established. MDSP NPs (∼54 nm), with near infrared absorption (∼853 nm), can be rapidly dissociated to generate oxygen in response to TME, whereby improving tumor hypoxia, in favor of effective drugs release and enhanced chemo/photodynamic therapy. Revealed by in vivo fluorescence and photoaccoustic imaging, MDSP NPs are preferential accumulated at tumor site. Confirmed by photothermal imaging, MDSP NPs can induce hyperthermia to relieve hypoxia, promote the uptake of therapeutic nanoparticles, and further reduce the resistance and improve the therapeutic efficiency. As a result, a remarkable synergistic tumor chemo/photodynamic/photothermal therapy with hydrangea-structured TME responsive oxygen-self-generation nanoplatform is confirmed by both in vitro and in vivo studies, testifying its great potential for hypoxic tumor treatment in clinical application.

Keywords: Chemotherapy; Hypoxia; Photodynamic therapy; Photothermal therapy; Tumor microenvironment responsive.

Publication types

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

MeSH terms

Animals
Boron Compounds / chemistry
Cell Survival / drug effects
HCT116 Cells
Humans
Hydrangea / chemistry*
Hydrogen Peroxide / toxicity
Mice, Inbred BALB C
Mice, Nude
Multimodal Imaging*
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Neoplasms / diagnosis*
Neoplasms / therapy*
Photosensitizing Agents / therapeutic use
Spectrophotometry, Ultraviolet
Temperature
Tumor Hypoxia*
Tumor Microenvironment*

Substances

4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
Boron Compounds
Photosensitizing Agents
Hydrogen Peroxide