title: Enhanced cytotoxic effect of camptothecin nanosponges in anaplastic thyroid cancer cells in vitro and in vivo on orthotopic xenograft tumors.
abstract: Anaplastic carcinoma of the thyroid (ATC) is a lethal human malignant cancer with median survival of 6 months. To date, no treatment has substantially changed its course, which makes urgent need for the development of novel drugs or novel formulations for drug delivery. Nanomedicine has enormous potential to improve the accuracy of cancer therapy by enhancing availability and stability, decreasing effective doses and reducing side effects of drugs. Camptothecin (CPT) is an inhibitor of DNA topoisomerase-I with several anticancer properties but has poor solubility and a high degradation rate. Previously, we reported that CPT encapsulated in β-cyclodextrin-nanosponges (CN-CPT) increased solubility, was protected from degradation and inhibited the growth of prostate tumor cells both in vitro and in vivo. The aim of this study was to extend that work by assessing the CN-CPT effectiveness on ATC both in vitro and in vivo. Results showed that CN-CPT significantly inhibited viability, clonogenic capacity and cell-cycle progression of ATC cell lines showing a faster and enhanced effect compared to free CPT. Moreover, CN-CPT inhibited tumor cell adhesion to vascular endothelial cells, migration, secretion of pro-angiogenic factors (IL-8 and VEGF-α), expression of β-PIX, belonging to the Rho family activators, and phosphorylation of the Erk1/2 MAPK. Finally, CN-CPT significantly inhibited the growth, the metastatization and the vascularization of orthotopic ATC xenografts in SCID/beige mice without apparent toxic effects in vivo. This work extends the previous insight showing that β-cyclodextrin-nanosponges are a promising tool for the treatment of ATC.
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Casimiro Luca
authors.initials: CL
authors.lastname: Gigliotti
authors.affiliation: b Department of Drug Science and Technology , University of Torino , Torino , Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Ferrara
authors.affiliation: c Department of Molecular Biotechnology and Health Sciences , University of Torino , Torino , Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Occhipinti
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Boggio
authors.affiliation: d Department of Clinical and Biological Sciences , University of Torino , Torino , Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barrera
authors.affiliation: d Department of Clinical and Biological Sciences , University of Torino , Torino , Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pizzimenti
authors.affiliation: c Department of Molecular Biotechnology and Health Sciences , University of Torino , Torino , Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Giovarelli
authors.affiliation: b Department of Drug Science and Technology , University of Torino , Torino , Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fantozzi
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiocchetti
authors.affiliation: b Department of Drug Science and Technology , University of Torino , Torino , Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Argenziano
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Nausicaa
authors.initials: N
authors.lastname: Clemente
authors.affiliation: e Department of Chemistry , University of Torino , Torino , Italy , and.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trotta
authors.affiliation: f Department of Medical Sciences , University of Torino , Torino , Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchiò
authors.affiliation: f Department of Medical Sciences , University of Torino , Torino , Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.affiliation: a Department of Health Sciences , Interdisciplinary Research Center of Autoimmune Diseases, UPO , Novara , Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Dianzani
authors.affiliation: b Department of Drug Science and Technology , University of Torino , Torino , Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: b Department of Drug Science and Technology , University of Torino , Torino , Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dianzani
mesh_terms: D000818:Animals; D002166:Camptothecin; D045744:Cell Line, Tumor; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D065646:Thyroid Carcinoma, Anaplastic
chemical_list: D002166:Camptothecin
keywords: Camptothecin; anaplastic thyroid carcinoma; cell adhesion; cell migration; β-cyclodextrin-nanosponges