title: Doxorubicin-Loaded Nanobubbles Combined with Extracorporeal Shock Waves: Basis for a New Drug Delivery Tool in Anaplastic Thyroid Cancer.
abstract: No standard chemotherapy is available for anaplastic thyroid cancer (ATC). Drug-loaded nanobubbles (NBs) are a promising innovative anticancer drug formulation, and combining them with an externally applied trigger may further control drug release at the target region. Extracorporeal shock waves (ESWs) are acoustic waves widely used in urology and orthopedics, with no side effects. The aim of the present work was to combine ESWs and new doxorubicin-loaded glycol chitosan NBs in order to target doxorubicin and enhance its antitumor effect in ATC cell lines.
  
  
  
  CAL-62 and 8305C cells were treated with empty NBs, fluorescent NBs, free doxorubicin, and doxorubicin-loaded NBs in the presence or in the absence of ESWs. NB entrance was evaluated by fluorescence microscopy and flow cytofluorimetry. Cell viability was assessed by Trypan Blue exclusion and WST-1 proliferation assays. Doxorubicin intracellular content was measured by high-performance liquid chromatography.
  
  
  
  Treatment with empty NBs and ESWs, even in combination, was safe, as cell viability and growth were not affected. Loading NBs with doxorubicin and combining them with ESWs generated the highest cytotoxic effect, resulting in drug GI50 reduction of about 40%. Mechanistically, ESWs triggered intracellular drug release from NBs, resulting in the highest nuclear drug content.
  
  
  
  Combined treatment with doxorubicin-loaded NBs and ESWs is a promising drug delivery tool for ATC treatment with the possibility of using lower doxorubicin doses and thus limiting its systemic side effects.
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Francesca
authors.initials: F
authors.lastname: Marano
authors.affiliation: 2 Department of Drug Science and Technology, University of Turin , Turin, Italy .
authors.forename: Monica
authors.initials: M
authors.lastname: Argenziano
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Roberto
authors.initials: R
authors.lastname: Frairia
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Aloe
authors.initials: A
authors.lastname: Adamini
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Ornella
authors.initials: O
authors.lastname: Bosco
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Letizia
authors.initials: L
authors.lastname: Rinella
authors.affiliation: 3 Oncological Endocrinology, AO Città della Salute e della Scienza di Torino, Turin, Italy .
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fortunati
authors.affiliation: 2 Department of Drug Science and Technology, University of Turin , Turin, Italy .
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: 1 Department of Medical Sciences, University of Turin , Turin, Italy .
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: Catalano
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D000074059:Extracorporeal Shockwave Therapy / Q000379:methods*; D006801:Humans; D065646:Thyroid Carcinoma, Anaplastic / Q000188:drug therapy / Q000628:therapy*; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin