(292a) Award Submission: Tracking Biodistribution of NIR-Labeled Polymeric Micelles of Varying Shape and Surface Charge

Polymeric micelles synthesized from the self-assembly of amphiphilic block copolymers in solution have received increasing attention for applications in drug delivery. While the effect of size of these micelles on biodistribution and circulation kinetics has been well characterized, questions of the effects of micelle shape and surface charge remain largely unanswered. In this study, the shape of micellar carriers can be tuned from spheres to short and long cylinders (filomicelles) to bilayer vesicles (polymersomes) with simple changes in block copolymer architecture. In addition, the surface charge of polymersomes can be tuned to mimic the charge of red blood cells without chemical modification of the block copolymers. To efficiently track the biodistribution of these polymeric micelles in vivo, a near infrared fluorophore (NIRF) was non-covalently incorporated without affecting micelle morphology or surface charge. Preliminary results for the effect of surface charge on polymersomes indicate a distinct shift in the carrier biodistribution where anionic polymersomes are directed almost exclusively to the liver rather than the spleen and liver for neutral polymersomes. The tracking of NIRF-labeled filomicelles in healthy mice shows that the majority of carriers ? independent of length ? remained in circulation after 24 hours. In tumor-bearing mice, NIRF imaging suggests that filomicelles convect into a solid tumor and some fragments can penetrate into the tumor stroma, suggesting a mechanism by which filomicelles can effectively deliver encapsulated anti-cancer therapeutics to tumors [1].

[1] Christian DA, Cai S, Garbuzenko OB, Harada T, Zajac AL, Minko T, Discher DE. Molecular Pharmaceutics, DOI: 10.1021/mp900022m, (2009).