Zhu, JingyiWang, GuoyingAlves, Carla S.Tomás, HelenaXiong, ZhijuanShen, MingwuRodrigues, JoãoShi, Xiangyang2019-06-272019-06-272018Zhu, J.; Wang, G.; Alves, C. S.; Tomás, H.; Xiong, Z.; Shen, M.; Rodrigues, J. M. C.; Shi, X.; Multifunctional Dendrimer-Entrapped Gold Nanoparticles Conjugated with Doxorubicin for pH-Responsive Drug Delivery and Targeted Computed Tomography Imaging. Langmuir 2018, 34, 12428-12435.0743-7463http://hdl.handle.net/10400.13/2438Novel 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.engMultifunctional dendrimerGold nanoparticlesDoxorubicinpH-responsive drug deliveryDrug deliveryHydrogen-ion concentrationMetal nanoparticlesTheranostic nanomedicineComputed tomography imaging.Faculdade de Ciências Exatas e da EngenhariaCentro de Química da Madeirajournal article10.1021/acs.langmuir.8b02901