title: XAV939: from a small inhibitor to a potent drug bioconjugate when delivered by gold nanoparticles.
abstract: Nanoparticles as potential drug delivery vectors are drawing more attention every day. Here, we used gold nanopspheres (AuNSs) to selectively target the Wnt signaling pathway in human oral squamous cell carcinoma (HSC-3) cells. In a previously conducted study, XAV939, a small inhibiter, was found to strongly regulate the Wnt pathway by inhibiting the tankyrase enzyme and subsequent stabilization of cytoplasmic axin levels. In the present study, conjugating XAV939 molecules to AuNSs is found to enhance its potency by at least 100 times over its free form in killing HSC-3 cancer cells. Additionally, XAV 939 uptake studies have demonstrated an enhanced XAV939 bioconjugate delivery to the targeted cells compared to the passive cellular diffusion of the free drug at the same concentration. Furthermore, our study revealed that drug delivery and cytotoxicity are directly related to the size of the functionalized nanoparticles.
authors.affiliation: Laser Dynamic Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States.
authors.forename: Marwa M
authors.initials: MM
authors.lastname: Afifi
authors.affiliation: Laser Dynamic Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Austin
authors.affiliation: Laser Dynamic Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Mackey
authors.affiliation: Laser Dynamic Laboratory, School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332-0400, United States.
authors.forename: Mostafa A
authors.initials: MA
authors.lastname: El-Sayed
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006046:Gold / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D009062:Mouth Neoplasms / Q000473:pathology
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; C544261:XAV939; D006046:Gold