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Tumor-Microenvironment-Responsive Nanoconjugate for Synergistic Antivascular Activity and Phototherapy

Pingping Liang, Xiaoyu Huang, Ya Wang

  • 1Shaanxi Institute of Flexible Electronics (SIFE) , Northwestern Polytechnical University (NPU) , 127 West Youyi Road , Xi'an 710072 , China.

ACS Nano
|October 23, 2018
PubMed

Insights

This study introduces novel nanoparticles for cancer therapy. These nanoparticles combine photodynamic and photothermal treatments with antivascular action, effectively eliminating tumors without recurrence.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Solid tumor hypoxia and short singlet oxygen half-life limit photodynamic therapy (PDT) and photothermal therapy (PTT).
  • Up-regulation of heat shock proteins in tumors further complicates therapeutic efficacy.

Purpose of the Study:

  • To design and synthesize a near-infrared, carrier-free nanoconjugate for synergistic cancer treatment.
  • To develop a pH-responsive system with enhanced photodynamic and photothermal capabilities.
  • To incorporate an antivascular agent for targeted tumor destruction.

Main Methods:

  • Self-assembly approach to create biocompatible direct-acting antiviral (DAA) nanoparticles (NPs).
  • Utilized protonation of diethylaminophenyl units for amplified pH-responsive photodynamic/photothermal performance.
  • Incorporated 5,6-dimethylxanthenone-4-acetic acid as an antivascular agent, released via ester bond hydrolysis.

Main Results:

  • DAA NPs exhibited amplified pH-responsive photodynamic and photothermal behavior in acidic tumor microenvironments.
  • Targeted release of the antivascular agent in endothelial cell endosomes effectively destroyed tumor vasculature.
  • Demonstrated specific targeting of vascular endothelial cells and tumor lysosomes in vitro.
  • Achieved complete tumor ablation with no recurrence or side effects in vivo.

Conclusions:

  • DAA NPs offer a promising synergistic approach combining antivascular therapy with PDT and PTT.
  • The pH-responsive and targeted drug release mechanism enhances cancer treatment efficacy.
  • This nanoconjugate strategy shows potential for effective and safe cancer ablation.
Keywords:
antivascular activityphotodynamic therapyphotothermal therapytargetedtumor microenvironment

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