Sonodynamic Therapy Using Protoporphyrin IX Conjugated to Gold Nanoparticles: An In Vivo Study on a Colon Tumor Model

Sonodynamic therapy is a physical treatment which utilizes ultrasound waves with an appropriate sensitizer such as protoporphyrin IX (PpIX). The activation of sensitizer depends on cavitation, and therefore, high intensity ultrasound is an important necessity. Beside, high intensity ultrasound can induce side effects on the healthy tissues which have surrounded tumor. The particles in a liquid decrease the ultrasonic intensity threshold needed for onset of cavitation. The non-radiative relaxation time of PpIX in the presence of gold nanoparticles (GNP) is longer than the similar time without GNP.

This study was conducted on colon carcinoma tumor in BALB/c mice. The tumors were induced by subcutaneous injection of CT26 cells. Ultrasound irradiation were performed on tumors 24 hr after the injection of PpIX into GNPs. Antitumor effects were estimated by measuring tumor relative volume, doubling time and time being five times of the tumors and by calculating the average survival time of tumor-bearing mice after treatment.

There is no inhibitory effect in control group. Ultrasound irradiation alone showed a slight antitumor effect which was enhanced by ultrasound plus PpIX (SDT). The synergistic inhibitory effect was significant when ultrasound plus PpIX was conjugated to GNPs.

Our experiments suggested a significant synergistic effect of ultrasound combined with Au-PpIX that reduced tumor relative volume and increased average animal survival fraction. This effect was obviously stronger than ultrasound alone and synergistic effect of ultrasound combined with PpIX.