A novel strategy for efficient "nanodelivery" of
DNA-cleaving molecules for
breast cancer regression is presented here. The synthetic methodology can be tweaked for controlled delivery and better bioavailability of effective doses of these
DNA-cleaving agents through a defined self-assembled polymeric nanoarchitecture. In vitro studies in ER+ and ER-
breast cancer human cell lines confirmed an efficient "nano"-delivery of
DNA-cleaving molecules and indicated their capability to mediate oxidative damage to nucleobases and/or to the
2-deoxyribose moiety. Prepared E-poly-
DNA-cleaver and C-poly-
DNA-cleaver were found to be interacting with plasmid
DNA pBR322 (pDNA) and active to cause oxidative cleavage of pDNA in the presence of
ascorbic acid and H2O2. They were found to be significantly active as
DNA cleaving agents in vitro and showed highly improved
cancer regression in MCF-7 and MD-MB231
cancer cells compared to small molecule
DNA cleaver. Surface conjugated nanoparticles were found to be more effective than noncovalent encapsulation and the small molecule agent, whereas in all the cases RCM was significantly inactive toward DNA cleavage. Blood contact complement activation properties were evaluated to gauge their likelihood to promote acute toxicity following systemic administration. The complement activation analyses together with the blood smear study confirm the feasibility of using these poly-
DNA-cleavers without risk of induced immune response.