以磁纳米粒为核的pH敏感型聚谷氨酸树状分子药物载体

报道了一种新的肽类树枝状分子改性磁性纳米药物载体.以天然氨基酸L-谷氨酸为原料,通过收敛法合成了聚(L-谷氨酸)树状分子,将多巴胺配体键合到聚(L-谷氨酸)树状分子上,用核磁(1H-NMR)、质谱(MS)对合成出的树状分子配体进行了表征,然后通过配体交换对四氧化三铁磁纳米粒表面进行多功能化.以阿霉素为模型药物通过pH敏...

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

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.