Reduction-degradable PEG-b-PAA-b-PEG triblock copolymer micelles incorporated with MTX for cancer chemotherapy

Reduction-breakable core-shell type polymeric micelles from reduction-degradable amphiphilic polyethylene glycol-b-polyamide amine-b-polyethylene glycol triblock copolymers (PEG-b-PAA-b-PEG) were prepared as new drug carriers of methotrexate (MTX) for cancer chemotherapy. The PEG-b-PAA-b-PEG copolymers were synthesized in a simple one-step process under mild condition through Michael addition. Spherical micelles with diameters ranging from 65 to 123nm were successfully fabricated from the copolymers. These micelles could effectively encapsulate the anti-cancer drug MTX in the core with drug loading content around 13%. The incorporation of MTX resulted in a little size increase but did not influence the morphology of micelles. The drug was hardly released from the micelles in normal condition without DDT as the reductant, but fast released up to 100% within 24h when the structure of micelle core was broken in the presence of DTT, thus provided a potential tool for tumor targeting delivery of MTX using the higher concentration of reductant in tumor tissues. The proliferation inhibition experiments demonstrate that MTX-encapsulated micelles show significant cytotoxicity to KB, HepG2 and 4T1 tumor cells, especiallythe 4T1 cells.