Design, Synthesis And Biological Applications Of Iron/iron Oxide Core/shell Nanoparticles

In order to achieve triple functional properties in one entity-targeting, PTT,andimaging for cancer treatment, We design iron/iron oxide core/shell nanoparticles thatpossess a good dispersion, low toxicity, good biocompatibility and high saturationmagnetization, high photothermal conversion efficiency as a new targeted agents usedin photothermal cancer therapy.This thesis is focused on two aspects:1)magnetictargeting iron/iron oxide core/shell nanoparticles are designed and synthesized to bein one entity-targeting,PTT,and imaging aimed to tumor ablation;2)tumor targetingiron/iron oxide core/shell nanoparticles are designed and synthesized to U-87cells toimprove highly selectively to tumor cells, thus leading to low systematic toxicity.1.synthesis and biological applications of magnetic targeting PEGylated iron/ironoxide core/shell nanoparticlesA good dispersion oil-soluble iron/iron oxide core/shell nanoparticles weresynthesized by the pyrolysis methodology via the precursor of iron pentacarbonyl, Toendow the NPs with water solubility and biocompatibility, PEG chains were anchoredon the surface of Fe@Fe₃O₄NPs via coordination interaction between PEGylateddopamine and the Fe₃O₄surface, a diameter of approximately14nm were synthesized.The formed iron/iron oxide core/shell nanoparticles are water-dispersible, stable, andalso biocompatible when the Fe concentration is below200μg/mL in24hours asconfirmed by cytotoxicity assay. Hysteresis loop measurement shows the maximumsaturation magnetization can reach80emu/g. And relaxivity measurements showsthat the iron/iron oxide core/shell Nps have a T2relaxivity（r2） of164mM/s on the0.5T scanner to156mM/s on the3.0T scanner, suggesting a possibility to use the Npsas a magnetic targeting agents and T2contrast agents. They also exhibit a highphotothermal conversion efficiency to that of Au nanorods and the capacity of photothermal stability is better than that of Au nanorods, All of this provide a reliabledata to make iron/iron oxide core/shell nanoparticles as a photothermal therapy agent.In addition, We greatly proved that iron/iron oxide core/shell nanoparticles canpossess triple functional properties in one entity-targeting, PTT,and imaging forcancer treatment via MRI imaging, confocal microscopic imaging, flowcytometry,photothermal imaging in mice, effect of photothermal treatment in miceand analysis of tumor biopsies in mice.2.synthesis and biological applications of tumor targeting PEGylated andRGDylated iron/iron oxide core/shell nanoparticlesIn this part, we still synthesized oil-soluble iron/iron oxide core/shellnanoparticles by the pyrolysis methodology via the precursor of iron pentacarbonyl.We made PEG chains anchored on the surface of Fe@Fe₃O₄NPs via coordinationinteraction between PEGylated dopamine and the Fe₃O₄surface to improve the watersolubility and biocompatibility, then we connected an arginine-glycine-aspartic acid（RGD） peptide as a targeting ligand on to their surface make the Nps have an averagesize of14nm and hydrated radius of180nm.The formed iron/iron oxide core/shellnanoparticles are biocompatible when the Fe concentration is below200μg/mL in24hours as confirmed by cytotoxicity assay. Relaxivity measurements shows thatiron/iron oxide core/shell Nps have a T2relaxivity（r2） of138mM/s on the0.5Tscanner. We also proves that iron/iron oxide core/shell nanoparticles is a goodphotothermal therapy agent via several experiments such as photothermal effect insolution.Iron/iron oxide core/shell nanoparticles can targeted MR imaging andphotothermal therapy of tumor cells via targeted photothermal treatment experimentover-expressing high affinityαvβ3integrin in vitro.