R.J. Cavazos, C.S. Morrison, J.B. Lampe, D.T. Nguyen, A.N. Harris, B.K. McFarlin, R.A. Petros
University of North Texas, United States
pp. 49 - 51
Keywords: albumin, cobalt, nanoparticle, SN-38, topotecan, gastric carcinoma
Alfred Werner, the father of inorganic chemistry, received the Nobel Prize in 1913 for his pioneering work in formulating a theory to describe bonding patterns for coordination compounds. A number of complexes studied were amine complexes of cobalt, which are easily synthesized and quite robust. We have begun applying this classic coordination chemistry to the bioconjugation of amine-containing (bio)molecules in the context of targeted drug delivery. In addition to being an efficient conjugation strategy, the chemistry is completely reversible allowing for the synthesis of redox responsive materials. Co(3+) is inert to ligand exchange; however, upon reduction to Co(2+) labile ligand exchange occurs, which provides an opportunity to capitalize on the reducing nature of cytosol and hypoxic tumor microenvironments as stimuli for degradation of the delivery vector and concomitant release of therapeutic payload. We have applied this methodology to the synthesis of albumin nanoparticles (10-500 nm) and examined particle uptake in gastric carcinoma cells (SNU-5) by image-based flow cytometry. The particles were further loaded with camptothecin derivatives via either passive encapsulation (SN-38), or cobalt-mediated bioconjugation to albumin (topotecan). Details of drug loading and release will be discussed along with preliminary cytotoxicity results.