The use of Werner complexes as remarkably versatile bioconjugation reagents in the synthesis of redox repsonsive albumin nanoparticles containing camptothecin derivatives

摘要

We have begun applying 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.