Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol...Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.展开更多
基金This research was supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Education,Science and Technology(No.2012R1A2A2A02044997 and No.2012R1A1A1039059).
文摘Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.
