POLY(L-GLUTAMIC ACID) DENDRON BASED pH SENSITIVE DRUG CARRIER WITH MAGNETIC NANOPARTICLE CORE

Abstract

Recent advances on targeted drug delivery systems which interact with intracellular components or events such as pH change have been an exciting focus for biomaterials scientists.In present work,poly(L-glutamic acid) peptide dendron was synthesized,and dopamine was immobilized on it as the ligand to substitute the oleic acid on the surface of hydrophobic Fe3O4 magnetic nanoparticles via ligand exchange.The anticancer drug doxorubicin(DOX) was conjugated to the peripheral functional groups of poly(L-glutamic acid) dendron with pH sensitive hydrazine linkers to construct magnetic drug loaded nanocarriers.The structure of the dendron ligand was determined by 1H-NMR and ESI-TOF-MS.The poly(L-glutamic acid) dendron modified magnetic nanoparticles were characterized by TEM,SEAD,DLS and FTIR.The results showed that the crystalline structure of the magnetic cores were not varied after the ligand exchange,the modified magnetic nanoparticles exhibited excellent aqueous dispersity and stability.The DOX loading of modified magnetic nanoparticles with the average size of ca.63 nm was 52.4 mg·g-1.The release rate of DOX from the magnetic nanocarrier in the acid medium(pH=5.0) was dramatically higher than that in the physiological conditions(pH=7.4).The poly(L-glutamic acid) dendron modified magnetic nanoparticles showed excellent biocompatibility and low cytotoxicity in vitro,and the Fe3O4-G2(Glu)-DOX conjugate was efficient in inhibiting the proliferation of HeLa cells.Therefore,the pH sensitive peptide modified magnetic nanoparticle as a nanocarrier could be effectively utilized in drug delivery system.