Development of a Composite of Polypyrrole-Coated Carbon Nanotubes as a Sonosensitizer for Treatment of Melanoma Cancer Under Multi-Step Ultrasound Irradiation

Abstract

Sonodynamic therapy (SDT) has established a novel route for treating solid cancers. Low-intensity ultrasound irradiation accompanied by a sonosensitizer has revealed remarkable advantages for cancer therapy such as targeted uptake, access to deeper tumors, insignificant side effects and invasiveness, compared with other therapeutic methods. In this study, we scrutinized synthesis and characterization of a polypyrrole-coated multi-walled carbon nanotubes composite (PPy@MWCNTs). PPy@MWCNTs can absorb ultrasound irradiation by both of its components, and it was introduced as a new sonosensitizer. The composite was characterized by field emission scanning electron microscopy (FESEM), and its ability to temperature elevation was explored. FESEM images revealed that PPy@MWCNTs comprised nanotubes of 36.3 ± 5.1 nm in diameter with up to several micrometer in length. Ultrasound irradiation at 1 MHz and 1.0 W cm−2 for 60 s in four steps led to an efficient SDT in vitro (16.3 ± 2.8°C temperature increment for 250 μg mL−1 of PPy@MWCNTs), in C540 (B16/F10) cell line and a melanoma tumor model in male balb/c mice. In vitro examinations revealed that PPy@MWCNTs represented a concentration-dependent cytotoxicity on multi-step ultrasound irradiation (a cell viability of 8.9% for 250 μg mL−1 of PPy@MWCNTs). Histologic analyses and tumor volume decrement after 10 d revealed detrimental SDT effects of PPy@MWCNTs on tumors (75% necrosis and 50% decrement in tumor volume). Thermal effects and reactive oxygen species generation were the reasons of the working function of PPy@MWCNTs in SDT.