Control of in vivo blood clearance time of polymeric micelle by stereochemistry of amphiphilic polydepsipeptides

Polymeric micelle, “Lactosome,” is composed of amphiphilic polydepsipeptide with a hydrophobic block of helical poly(l-lactic acid) (PLLA) and a hydrophilic block of poly(sarcosine). Lactosome was labeled by incorporation of poly(lactic acid) having a near-infrared fluorescence (NIRF) chromophore, and studied on blood clearance and tumor imaging. In vivo blood clearance time of Lactosome was prolonged with incorporation of poly(d-lactic acid) (PDLA), but decreased with poly(d,l-lactic acid) (PDLLA). NIRF imaging with applying these Lactosomes to tumor-bearing mice revealed that the tumor/background intensity ratio increased with incorporation of PDLLA. Stereochemistry in the hydrophobic core of self-assemblies is thus an important factor for determining physical stability in the blood stream and consequently contrast in imaging. [Display omitted]