A novel nanosonosensitizer for sonodynamic therapy: in vivo study on a colon tumor model.

OBJECTIVES

The particles in a liquid decrease the ultrasonic intensity threshold needed for cavitation onset. In this study, a new nanoconjugate composed of protoporphyrin IX and gold nanoparticles was used as a nucleation site for cavitation. The nonradiative relaxation time of protoporphyrin IX in the presence of gold nanoparticles is longer than the similar time without gold nanoparticles.

METHODS

This study was conducted on colon carcinoma tumors in BALB/c mice. The tumor-bearing mice were randomly divided into 6 groups (each containing 15 mice): (1) control, (2) protoporphyrin IX, (3) gold nanoparticle-protoporphyrin IX conjugate, (4) ultrasound alone, (5) ultrasound + protoporphyrin IX, and (6) ultrasound + gold nanoparticle-protoporphyrin IX conjugate. In the respective groups as indicated above, protoporphyrin IX or the gold nanoparticle-protoporphyrin IX conjugate was injected into the tumors. Ultrasound irradiation was performed on the tumors 24 hours after injection. Antitumor effects were estimated by evaluation of the relative tumor volume, doubling time, and 5-folding time for the tumors after treatment. The cumulative survival fraction of the mice and percentage of the lost tissue volume (treated) were also assessed in the different groups.

RESULTS

A significant difference in the average relative volumes of the tumors 13 days after treatment was found between the ultrasound + gold nanoparticle-protoporphyrin IX group and the other groups (P < .05). The longest doubling and 5-folding times were observed in the ultrasound + gold nanoparticle-protoporphyrin IX and ultrasound + protoporphyrin IX groups.

CONCLUSIONS

Protoporphyrin IX conjugated to gold nanoparticles has been introduced as a promising compound and a new sonosensitizer for improving the tumor response to sonodynamic therapy by reducing the relative tumor volume and increasing the cumulative survival fraction.