DNA damage induced by micellar-delivered doxorubicin and ultrasound: comet assay study

• Published in: Cancer letters 2000-06, Vol.154 (2), p.211-216
• Main Authors: Husseini, Ghaleb A., El-Fayoumi, Refaat I., O'Neill, Kim L., Rapoport, Natalya Y., Pitt, William G.
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Comet Assay; DNA Damage; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Delivery Systems; HL-60 Cells; Humans; Medical sciences; Micellar drug delivery; Micelles; Pharmacology. Drug treatments; Time Factors; Ultrasonography; Ultrasound
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(00)00399-2

To minimize adverse side effects of chemotherapy, we have developed a micellar drug carrier that retains hydrophobic drugs, and then releases the drug by ultrasonic stimulation. This study investigated the DNA damage induced by doxorubicin (DOX) delivered to human leukemia (HL-60) cells from pluronic P-105 micelles with and without the application of ultrasound. The comet assay was used to quantify the amount of DNA damage. No significant DNA damage was observed when the cells were treated with 0.1, 1 and 10 wt% P-105 with or without ultrasound (70 kHz, 1.3 W/cm 2) for 1 h or for up to 3 h in 10 wt% P-105. However, when cells were incubated with 10 μg/ml free DOX for up to 9 h, DNA damage increased with incubation time ( P=0.0011). Exposure of cells to the same concentration of DOX in the presence of 10-wt% P-105 showed no significant DNA damage for up to 9 h of incubation. However, when ultrasound was applied, a rapid and significant increase in DNA damage was observed ( P=0.0001). The application of ultrasound causes the release of DOX from micelles or causes the HL-60 cells to take up the micelle encapsulated DOX. Our experiments indicated that the combination of DOX, ultrasound and pluronic P105 causes the largest DNA damage to HL-60 cells. We believe that this technique can be used for controlled drug delivery.