The effect of umbrella-type branching on the blood circulation and tumor targeting of star-branched PLA-PMPC copolymer micelles

The effect of branching on the blood circulation and tumor targeting of polymer nanovehicles in vivo was investigated in this study. For the purpose, star-branched poly(lactic acid) and poly(2-methacryloyloxyethyl phosphorylcholine)(PLA-PMPC)copolymers with umbrella-type AB_3,(AB_3)_2, and(AB_3)_3 architecture were synthesized by branching at the PLA core. Micelles self-assembled from these copolymers were used to evaluate the effect of core branching on blood circulation and tumor targeting. The results showed that branching changed the behavior of polymeric self-assembly in solution, thereby changing the size and surface anti-fouling performance of the polymeric micelles. Moreover, star-branched copolymer micelles with a higher branching degree allowed their payload to persist better in blood(half-time prolonged from 7.1, 8.6 to 13.8 h) and for a 1.72-fold higher content at the tumor site. These studies suggest that raising the branching degree of amphiphilic copolymer potentially offers a promising strategy for the design of carriers capable of enhanced circulation and targeting in vivo.