Authors: E. Holler, Hui Ding, R. Patil, J. Portilla, S. Inoue, P. Gangulum, S.E. McNeil, A. Patri, M.A. Dobrovolskaia, K.L. Black, J.Y. Ljubimova
Affilation: Cedars-Sinai Medical Center, United States
Pages: 210 - 213
Keywords: anticancer nanodrug, 3rd. generation, polymer, toxicity
A polyanionic drug carriers is presented that penetrates biobarriers and targets molecular cancer markers of human breast and brain cancer. The carrier platform is poly(beta-L-malic acid) (PMLA), which is highly water soluble and biodegradable to CO2 and H2O. The polycarboxylate is an efficient monomolecular carriers with a high content of reactive groups by mass, which allows chemical attachment of multiple drug(s), targeting molecules, membrane disrupting molecules, imaging and protecting groups. The nanoconjugates are highly diffusible with half-lives of 12-24 hrs after systemic application. Because of the versatile combination of functional groups, we call this the third generation of nanoconjugates ready for combination therapy and personalized medicine. We have synthesized nanodrugs highly efficient for systemic treatment of primary brain cancers, HER2-positive breast cancer, triple negative breast cancer, and brain metastases from breast and lung tumors. Results of human standard in vitro compatibility tests examining kidney- and liver cells, platelet aggregation, erythrocyte hemolysis, plasma coagulation, macrophage activation (NO secretion, phagocytesis), complement activation (immune response), leucocyte proliferation (immune response), DC maturation regulating HLA-DR, HLA-ABC, CD80, CD83 (immune response) and on mouse in vivo biocompatibility of PMLA and lead nanoconjugates all show absence of toxic and other effects following FDA protocols.