A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells
(0) One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells,which leads to non-specific uptake of nanocarriers by non-cancerous cells.Here,we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand.The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers.The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions.Typically.Fe3O4 nanocrystals(FN)as magnetic resonance imaging(MRI)contrast agents were encapsulated into albumin nanoparticles(AN),and then folic acid(FA)and pH-sensitive polymers(PP)were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles.Fourier transform infrared spectroscopy(FT-IR),dynamic light scattering(DLS).transmission electron microscope(TEM)and gel permeation chromatography(GPC)results confirm successful construction of PP-FA-AN-FN.According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5.the weight ratio of conjugated PP to nanoparticle FA-AN-FN(i.e.graft density)and the molecular weight of PP(i.e.graft length)arc optimized lo be 1.32 and 5.7 kDa.respectively,in vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5.In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the nonspecific uptake of the PP-FA-AN-FN by non-cancerous cells.Therefore,our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent.
Trojan-horse targeting strategy MRI contrast agents Active targetability to cancer cells Non-specific uptake by non-cancerous cells
Zheyu Shen Hao Wu Sugeun Yang Xuehua Ma Zihou Li Mingqian Tan Aiguo Wu
Division of Functional Materials and Nano Devices,Ningbo Institute of Materials Technology & Enginee Division of Biotechnology,Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian,11 Department of New Drug Development,School of Medicine,Inha University,Incheon,400-712,South Korea
国内会议
北京
英文
100-110
2015-10-09（万方平台首次上网日期，不代表论文的发表时间）