Protease Mediated Anti-Cancer Therapy

Abstract

A new approach to selective photodynamic therapy (PDT) was developed by designing chlorin e6 containing macromolecules which are sensitive to tumorassociated proteases. The agents are non-toxic in their native state but become fluorescent and produce singlet oxygen (SOG) upon protease conversion. Coupled with optimized delivery systems we demonstrate that a) the agents efficiently accumulate in tumors due to the enhanced permeability and retention effect, b) the agents are locally activated by proteases, c) local drug concentrations can be measured by quantitative fluorescence tomography, and d) light treated tumors show reduced growth. A single low dose of PDT (0.125 mg Ce6 equivalent/kg) was sufficient to suppress tumor growth by over 50%. Activatable SOG agents provide increased efficacy with reduced toxicity, and it could become a powerful photodynamic therapy.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2006
Accession Number
ADA458446

Entities

People

  • Ching-Hsuan Tung

Organizations

  • Massachusetts General Hospital

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Physiological Processes
  • Chemical Synthesis
  • Chemistry
  • Fluorescence
  • Health Services
  • Laser Therapy
  • Mass Spectrometry
  • Molecules
  • Optical Properties
  • Organic Chemistry
  • Oxygen
  • Peptides
  • Physical Properties
  • Quantum Yields
  • Spectra
  • Statistical Analysis

Readers

  • Medical Imaging.
  • Molecular and Cellular Biochemistry
  • Optical Physics and Photonics.