Resulting heterobifunctional prodrugs all formed nanoparticles (Figure ), with diameters in the 99-142 nm range but exhibited different Gem release kinetics in human serum depending on the polymer prodrug structure. While the release of Gem from Gem-amide-PI nanoparticles reached 6 % after 24 h, it was considerably lowered (0.5-2 %) with all heterobifunctional polymer prodrug nanoparticles (Figure ). Interestingly, co-nanoprecipitation of monofunctional polymer prodrugs (i.e., Gem-amide-PI and PI-amide-Dox) resulted in Gem release similar to that of Gem-amide-PI nanoparticles (~8 %). These results suggested that