title: Targeting Taxanes to Castration-Resistant Prostate Cancer Cells by Nanobubbles and Extracorporeal Shock Waves.
abstract: To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect.
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Marano
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Rinella
authors.affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Argenziano
authors.affiliation: Department of Drug Science and Technology, University of Turin, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cavalli
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sassi
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Amelio
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Battaglia
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Bosco
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Peluso
authors.affiliation: Oncological Endocrinology, AO Città della Salute e della Scienza di Torino, Turin, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Fortunati
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frairia
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Maria Graziella
authors.initials: MG
authors.lastname: Catalano
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry; D065546:Drug Liberation / Q000528:radiation effects; D019220:High-Energy Shock Waves; D006801:Humans; D008297:Male; D049329:Nanostructures / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D043823:Taxoids; C118638:glycol-chitosan; D000077143:Docetaxel; D048271:Chitosan; D017239:Paclitaxel