Browsing by Author "Xiong, Zhijuan"
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- Multifunctional dendrimer-entrapped gold nanoparticles conjugated with Doxorubicin for pH-responsive drug delivery and targeted computed tomography imagingPublication . Zhu, Jingyi; Wang, Guoying; Alves, Carla S.; Tomás, Helena; Xiong, Zhijuan; Shen, Mingwu; Rodrigues, João; Shi, XiangyangNovel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.
- Zwitterion-functionalized dendrimer-entrapped gold nanoparticles for serum-enhanced gene delivery to inhibit cancer cell metastasisPublication . Xiong, Zhijuan; Alves, Carla S.; Wang, Jianhua; Li, Aijun; Liu, Jinyuan; Shen, Mingwu; Rodrigues, João; Tomás, Helena; Shi, XiangyangWe demonstrate a novel serum-enhanced gene delivery approach using zwitterion-functionalized dendrimer-entrapped gold nanoparticles (Au DENPs) as a non-viral vector for inhibition of cancer cell metastasis in vitro. Poly(amidoamine) dendrimers of generation 5 decorated with zwitterion carboxybe taine acrylamide (CBAA) and lysosome-targeting agent morpholine (Mor) were utilized to entrap gold NPs. We show that both Mor-modified and Mor-free Au DENPs are cytocompatible and can effectively deliver plasmid DNA encoding different reporter genes to cancer cells in medium with or without serum. Strikingly, due to the antifouling property exerted by the attached zwitterion CBAA, the gene delivery efficiency of Mor-modified Au DENPs and the Mor-free Au DENPs in the serum-containing medium are 1.4 and 1.7 times higher than the corresponding vector in serum-free medium, respectively. In addition, the Mor-free vector has a better gene expression efficiency than the Mor-modified one although the Mor modification enables the polyplexes to have enhanced cancer cell uptake. Wound healing and hyperme thylated in cancer 1 (HIC1) protein expression assay data reveal that the expression of HIC1 gene in cancer cells enables effective inhibition of cell migration. Our findings suggest that the created zwitterion-functionalized Au DENPs may be employed as a powerful vector for serum-enhanced gene therapy of different diseases.