Browsing by Author "Zou, Yu"
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- Formation of functional polyetheylenimine-based nanogels for tumor MR imaging and chemotherapyPublication . Zou, Yu; Shi, Xiangyang; Tómás, Helena Maria Pires GasparNanogels (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.
- Polyethylenimine nanogels incorporated with ultrasmall iron oxide nanoparticles and doxorubicin for MR imaging-guided chemotherapy of tumorsPublication . Zou, Yu; Li, Du; Wang, Yue; Ouyang, Zhijun; Peng, Yucheng; Tomás, Helena; Xia, Jindong; Rodrigues, João; Shen, Mingwu; Shi, XiangyangDevelopment of versatile nanoplatforms for cancer theranostics remains a hot topic in the area of nanomedicine. We report here a general approach to create polyethylenimine (PEI)-based hybrid nanogels (NGs) incorporated with ultrasmall iron oxide (Fe3O4) nanoparticles (NPs) and doxorubicin for T1-weighted MR imaging guided chemotherapy of tumors. In this study, PEI NGs were first prepared using an inverse emulsion approach along with Michael addition reaction to cross-link the NGs, modified with citric acid stabilized ultrasmall Fe3O4 NPs through 1-ethyl-3-(3-(dimethylamino)- propyl) carbodiimide hydrochloride (EDC) coupling, and physically loaded with anticancer drug doxorubicin (DOX). The formed hybrid NGs possess good water dispersibility and colloidal stability, excellent DOX loading efficiency (51.4%), pH-dependent release profile of DOX with an accelerated release rate under acidic pH, and much higher r1 relaxivity (2.29 mM−1 s −1 ) than free ultrasmall Fe3O4 NPs (1.15 mM−1 s −1 ). In addition, in contrast to the drug-free NGs that possess good cytocompatibility, the DOX-loaded hybrid NGs display appreciable therapeutic activity and can be taken up by cancer cells in vitro. With these properties, the developed hybrid NGs enabled effective inhibition of tumor growth under the guidance of T1-weighted MR imaging. The developed hybrid NGs may be applied as a versatile nanoplatform for MR imaging-guided chemotherapy of tumors.