Size-dependent biodistribution and antitumor efficacy of polymer micelle drug delivery systems

The fate of polymeric micelles (PMs) is mainly determined by their physicochemical properties, such as particle size, shape, and surface potential. Of these factors, the size effect of PMs plays a fundamental role. In this study, four different sizes of PMs with fluorescence-labeling were prepared to study the size-dependent biodistribution profiles as well as the anti-tumor efficacy in H22-subcutaneous hepatoma-bearing mice. Both ex vivo tumor imaging and in vivo real-time near-infrared (NIR) dye-tracking experiments indicated that sub-100 nm PMs have a higher extent of accumulation in tumor sites than >100 nm PMs. For normal tissues, smaller PMs (35 nm) tend to accumulate in the kidney and larger PMs (145 nm) tend to be captured by the spleen and lung, while middle-sized PMs (75 and 115 nm) tend to accumulate in the liver. Finally, doxorubicin (Dox) was used as the model drug to study the size-dependent anti-tumor efficacy of Dox-loaded micelles with H22-bearing mice and the results indicated that the smallest micellar drugs exhibited the best tumor-growth inhibition effect.