Nitroxide radical-containing nanoparticles attenuate tumorigenic potential of triple negative breast cancer

Abstract

The critical importance of reactive oxygen species (ROS) as oncogene activators and essential secondary messengers in cancer cell survival have been widely reported. Since oxidative stress has been implicated as being pivotal in various cancers, antioxidant therapy seems an apt strategy to abrogate ROS-mediated cellular processes to attenuate cancers. We therefore synthesized ROS scavenging nitroxide radical-containing nanoparticles (RNPs); pH insensitive RNP^O and pH sensitive RNP^N, to impede the proliferative and metastatic characteristics of the triple negative breast cancer cell line, MDA-MB-231, both in vitro and in vivo. RNPs significantly curtailed the proliferative and clonogenic potential of MDA-MB-231 and MCF-7 cell lines. Inhibition of ROS-mediated migratory and invasive characteristics of MDA-MB-231, via down regulation of NF-κB and MMP-2, was also confirmed. Furthermore, a significant anti-tumor and anti-metastatic potential of RNPs was observed in an MDA-MB-231 mouse xenograft model. Such tumoricidal effects of RNPs were attained with negligible adverse effects, compared to conventional low molecular weight antioxidants, TEMPOL. Thus, the tumoricidal effects of RNPs are suggestive of insights on precedence of nanoparticle-based therapeutics over current low molecular weight antioxidants to curtail ROS-induced tumorigenesis of various cancers.

Keywords: Breast cancer; Nitroxide radical-containing nanoparticle; Reactive oxygen species; Redox cancer therapy; Tumorigenesis.