A tumor-targeting nano doxorubicin delivery system built from amphiphilic polyrotaxane-based block copolymers

Amphiphilic polyrotaxane (PR)-based block copolymers are synthesized by end-capping polypseudorotaxanes (PPRs) formed from distal 2-bromopropionyl terminated Pluronic F68 and a varying amount of β-cyclodextrins (β-CDs) using hydrophilic polymeric blocks of poly(ethylene glycol) methyl ether methacrylate (PEGMA) yielded via the in situ ATRP. To gain a tumor-targeting nano doxorubicin (DOX) delivery system for cancer chemotherapy, an active tumor-targeting ligand, folic acid (FA), is conjugated to the two ends of the resulting copolymers through “azide-ethylene click chemistry”. The conjugated copolymers enable to self-assemble into unique core-shell structured micelles in aqueous solution and to load DOX into the hydrophobic core. The drug loading content is increased from 2.0 wt% to 25.5 wt% with respect to the blank block copolymer most likely due to the hydrogen bond interaction between DOX and β-CDs threaded. After drug loading, the size of the micelles is enlarged from 120 nm to 220 nm in diameter as determined by dynamic light scattering (DLS) analysis. Moreover, these tumor-targeted polymeric micelles exhibit a slower and sustained DOX release behavior. The cell uptake and distribution, as well as the cytotoxicity of the polymeric micelles are also evaluated toward the MDA-MB-231 cells. The FA-conjugated PR-based block copolymer micelles appear to be internalized by the cancer cells via FA receptor mediated endocytosis; thus, they present enhanced cytotoxicity to the selected breast cancer cells.