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  • Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapy
    Publication . Zou, Yu; Shi, Xiangyang; Tómás, Helena Maria Pires Gaspar
    Nanogels (NGs) are three dimensional networks composed of hydrophilic or amphiphilic polymer chains, allowing for effective and homogeneous encapsulation of drugs, genes or imaging contrast agents for biomedical applications. Polyethylenimine (PEI), possessing sufficient positively charged amine groups, is an ideal platform for NG development. In this study, we synthesized PEI-based NGs loaded with both MR contrast agent ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and the anticancer drug doxorubicin (DOX) for tumor theranostics. The synthesis of PEI-based NGs was first carried out by an inverse mini-emulsion (water-in-oil, W/O) crosslinking strategy. Secondly, the NGs were conjugated with ultrasmall Fe3O4 NPs which was performed via a hydrothermal method through 1-ethyl-3(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) chemistry. Then the amine groups of the NGs were acetylated by acetic anhydride. The formed PEI-based NGs possess good dispersibility and cytocompatibility. The drug release profile was studied, as well as the impact of the environmental pH on the release rate of DOX. Results proved that the hybrid NGs facilitated a sustained release of DOX with a higher release rate under acidic pH. Furthermore, in vitro studies showed that Fe3O4/PEI-Ac NGs had no cytotoxicity towards 4T1 tumor cells, unlike Fe3O4/PEI-Ac NGs/DOX complexes and Free DOX. The PEI-based NGs presented significantly enhanced r1 relaxivity of 2.29 mM-1s-1 when compared to free ultrasmall Fe3O4 NPs (1.15 mM-1s-1), as well as excellent drug loading efficiency (51.4%). Strikingly, the NGs presented enhanced T1 MR imaging ability and a high therapeutic efficacy towards cancer cells in vitro and a xenografted tumor model in vivo.
    2019-09-26Master thesis Open access Show more