Radical dendrimer: bis-indolyl polyurethane dendrimers containing TEMPO radicals for inhibition of cancer cell growth

Abstract

Blocked isocyanate-terminated polyurethane dendrimers of first-generation (G1) to third-generation (G3) build-up with bis-indolyl units were subjected to urethane interchange reaction with 4-hydroxy-2, 2, 6, 6-tetramethylpiperidin-1-yloxyl (4-hydroxy TEMPO). The resulting free radical functionalized dendrimers were thoroughly characterized. The electron paramagnetic resonance (EPR)and vibrating sample magnetometer (VSM) results confirmed that these radical dendrimers are stable and paramagnetic. The cytotoxic effect of G1–G3 TEMPO-dendrimers was studied comprehensively across various cancer cell lines, encompassing human breast cancer (MCF-7 and MDA-MB-231), cervical cancer (SiHa), and lung cancer (A549 and NCI-H460), as well as normal lung epithelial cells (L132). It was observed that these TEMPO-dendrimers exerted cytotoxic effects in all cancer cell lines while demonstrating minimal impact on lung epithelial cells. Notably, MDA-MB-231 displayed heightened susceptibility to the TEMPO-dendrimers. Cell cycle analysis and morphological studies revealed that the TEMPO-dendrimers induced G1 phase cell cycle arrest and cell death specifically in breast cancer cells. Further investigations unveiled that these TEMPO-dendrimers triggered oxidative stress-mediated cell death specifically in breast cancer cells. All these findings suggest that the TEMPO radical dendrimers reported in this work exhibited cytotoxic effects in cancer cells by stimulating oxidative stress.