Yilmaz M.Karanastasis A.A.Chatziathanasiadou M.V.Oguz M.Kougioumtzi A.Clemente N.Kellici T.F.2020-03-262020-03-2620192576-6422https://dx.doi.org/10.1021/acsabm.8b00748https://hdl.handle.net/20.500.12395/38449Despite the anticancer potential of natural products (NPs), their limited bioavailability necessitates laborious derivatization or covalent conjugation to delivery vehicles. To unleash their potential, we developed a nanohybrid delivery platform with a noncovalently tunable surface. Initially, the active compound was encapsulated in a macrocycle, p-sulfonatocalix[4]arene, enabling a 62â000-fold aqueous solubility amplification as also a 2.9-fold enhancement in its cytotoxicity with respect to the parent compound in SW-620 colon cancer cells. A pH stimuli responsive behavior was recorded for this formulate, where a programmable release of quercetin from the macrocycle was monitored in an acidic environment. Then, a nanoparticle gold core was decorated with calixarene hosts to accommodate noncovalently NPs. The loaded nanocarrier with the NP quercetin dramatically enhanced the cytotoxicity (>50-fold) of the parent NP in colon cancer and altered its cell membrane transport mode. In vivo experiments in a mouse 4T1 tumor model showed a reduction of tumor volume in mice treated with quercetin-loaded nanoparticles without apparent toxic effects. Further analysis of the tumor-derived RNA highlighted that treatment with quercetin-loaded nanoparticles altered the expression of 27 genes related to apoptosis. © 2019 American Chemical Society.en10.1021/acsabm.8b00748info:eu-repo/semantics/closedAccessantitumor agentscalixarenecancerdrug deliveryIn vivonanoparticlesnatural productsquercetinArticle2727152725Q1