Targeting and anti-tumor effect of folic acid-labeled polymer-Doxorubicin conjugates with pH-sensitive hydrazone linker

Multifunctional micelles were successfully prepared by co-assembling a Doxorubicin-conjugated copolymer (mPEG-b-P(LA-co-ME/Dox), for antitumor properties) and a Rhodamine B-conjugated copolymer (mPEG-b-P(LA-co-ME/RhB), for imaging) with a folic acid (FA)-conjugated copolymer (FA-PEG-b-PLA, for targeting), respectively. DLS showed that the sizes of these micelles were in the range of 150-300 nm. Fluorescent imaging analysis based on the RhB signals of the isolated visceral organs showed that the micelles with or without FA moieties were mainly accumulated in the liver and in the tumor from 2 h post drug administration, maximized at ca. 6 h, and decayed afterwards. More FA-carrying micelles were accumulated in the tumor for a longer time compared to the micelles without FA moieties. Dox-containing micelles were used for tumor inhibition experiments in vivo and the results showed that the micelles with FA moieties exhibited better antitumor efficacy than those without FA and free Dox.