Construction of multifunctional/multimodality nanoparticles for cancer diagnosis and therapy has become an attractive area of investigation. In this report, we designed a multimodality nanoprobe for cell labeling, and can be detectable by both magnetic resonance and near infrared (NIR) fluorescence imaging. Multiple hydrophobic superparamagnetic iron oxide (SPIO) nanocrystals are self-assembled into nanocomposites in water phase with the help of partially alkylated hyperbranched polycation, polyethylenimine (PEI), which already conjugated with the indocyanine dye Cy5.5 and can be used for cell imaging under NIR fluorescence imaging. The amphiphilic PEI/SPIO nanocomposites have a strong T 2 relaxivity. The iron uptake process in MCF-7/Adr displays a time dependent behavior. Confocal laser scanning microscopy reveals that the nanoprobes are internalized into the cytoplasm of MCF-7/Adr after 24 h labeling. Both MR and NIR fluorescence imaging showed strong image contrast against unlabeled cells. Under a clinical MRI scanner, labeled cells in gelatin phantom present much darker images than controlled ones. The T2 relaxation rate of the labeled cells is 98.2 s 1 , significantly higher than that of the control ones of 2.3 s 1 . This study provides an important alternative to label MCF-7/Adr at optimized low dosages with high efficiency, and may be useful to label other biologically important cells and track their behaviors in vivo.
Dendritic cell(DC)-based vaccines have shown promising therapeutic results in cancer and some immune disorders.It is critical to track in vivo migration behaviours of DCs and monitor the whole process dynamically and non-invasively.Superparamagnetic iron oxide(SPIO)nanoparticles are chosen for DC labelling under magnetic resonance imaging(MRI)because of their proven biosafety as contrast agents.However,when used for cell labelling,sensitive biological indicators such as cell autophagy may be helpful to better understand the process and improve the probe design.Here,lactosylated N-Alkyl polyethylenimine coated SPIO nanoparticles are used for DC labelling.This probe shows satisfactory cell labelling efficiency and low cytotoxicity.In this study,autophagy was used as a key factor to understand how DCs react to nanoparticles after labelling.Our results demonstrate that the nanoparticles can induce protective autophagy in DCs,as inhibition of the autophagy flux could lead to cell death.Meanwhile,the nanoparticles induced autophagy could promote DC maturation which is an essential process for its migration and antigen presentation.Autophagy induced DC maturation is known to enhance the vaccine functions of DCs,therefore,our results suggest that beyond the MRI tracking ability,this probe might enhance therapeutic immune activation as well.
Taipeng ShenWencheng ZhuLi YangLi LiuRongrong JinJimei DuanJames M.AndersonHua Ai
Superparamagnetic iron oxide(SPIO)nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications.When covered with amphiphilic alkyl-polyethyleneimine(PEI),the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes.However,the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications.In this study,we used lactose to modify amphiphilic low molecular weight polyethylenimine(C_(12-)PEI_(2K))at different lactosylation degree.It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells,comparing to the unsubstituted ones.Besides,we found the PEI induced cell autophagy can be reduced via lactose modification,indicating the increased cell viability might rely on down-regulating autophagy.Thus,our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.
Jiuju DuWencheng ZhuLi YangChangqiang WuBingbing LinJun WuRongrong JinTaipeng ShenHua Ai
Superparamagnetic iron oxide （SPIO） nanoparticle clusters are one unique form which can enhance magnetic relaxivity and improve the magnetic resonance imaging contrast at the same iron concentration, comparing to single SPIO nanoparticles. Controlling of cluster size and other structural parameters have drawn great interests in this field to further improve their magnetic properties. In this study, we investigated how the interparticle distance （also known as neighbor distance） of SP10 nanocrystals within clusters affect their magnetic relaxation behaviors. To adjust the neighbor distance, different amount of cholesterol （CHO） was chosen as model spacers embedded into SPIO nanocluster systems with the help of amphiphilic diblock copolymer poly（ethylene glyco）-polyester. Small- angle X-ray scattering was applied to quantify the neighbor distance of SPIO clusters. The results demonstrated that the averaged SPIO nanocrystal neighbor distance of nan- oclusters increased with higher amount of added CHO. Moreover, these SPIO nanocrystal clusters had the promi- nent magnetic relaxation properties. Simultaneously, con- trolling of SPIO nanocrystal neighbor distance can regulate the saturation magnetization （Ms） and magnetic resonance （MR） T2 relaxation of the aggregation, and ultimately obtain better MR contrast effects with decreased neighbor distance.
Dan WangBingbing LinTaipeng ShenJun WuChunchao XiaBin SongHua Ai
