title: Tumor Spheroids as an in vitro model for determining the therapeutic response to proton beam radiotherapy and thermally sensitive nanocarriers.
abstract: Multicellular Tumor Spheroids (MCTS) strongly resemble tumor tissues, which makes them useful tools for radiation biology studies and screening of various chemotherapeutics. The goal of this pilot study was to use MCTS as an in vitro model to determine the response of cells to low temperature-sensitive liposomes (LTSLs) encapsulating doxorubicin (Dox) and proton beam radiotherapy (PBRT). Prior to treatment, MCTS were characterized for morphology and LTSLs were characterized for size, encapsulation efficiency, and ability to thermally release Dox (a model anticancer agent). Two groups of MCTS were treated with LTSL in combination with mild hyperthermia (40-42 °C) or PBRT alone in the presence of appropriate controls. Cytotoxic response was assessed after 48-72 h using an acid phosphatase assay. At 72 h, LTSL in combination with heat significantly reduced the viability of MCTS (15-30%) compared to the control (P < 0.05). A similar cytotoxic response was observed with PBRT treatment. The data suggest that like a monolayer cell culture, MCTS can be used to determine cytotoxic outcomes of thermal and proton therapy.
authors.affiliation: 1. Laboratory of Nanomedicine and Targeted Therapy, Department of Physiological Sciences, Center for Veterinary Health Sciences Oklahoma State University.
authors.forename: Lakmini K
authors.initials: LK
authors.lastname: Senavirathna
authors.forename: Ruchika
authors.initials: R
authors.lastname: Fernando
authors.forename: Danny
authors.initials: D
authors.lastname: Maples
authors.forename: Yuanshui
authors.initials: Y
authors.lastname: Zheng
authors.forename: Jerimy C
authors.initials: JC
authors.lastname: Polf
authors.forename: Ashish
authors.initials: A
authors.lastname: Ranjan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000528:radiation effects; D004358:Drug Therapy / Q000379:methods*; D008081:Liposomes / Q000528:radiation effects; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D061766:Proton Therapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin
keywords: Drug delivery; Liposomes; Proton beam radiotherapy; Tumor spheroids
references.citation: Mol Pharm. 2010 Dec 6;7(6):2006-19
references.pmid: 20957996
references.citation: Nanoscale. 2013 Jan 7;5(1):143-6
references.pmid: 23154390
references.citation: J Control Release. 2012 Nov 28;164(1):95-102
references.pmid: 22974689
references.citation: J Control Release. 2012 Mar 28;158(3):487-94
references.pmid: 22210162
references.citation: Int J Hyperthermia. 2011;27(2):140-55
references.pmid: 21314334
references.citation: Cancer Res. 2013 Jan 1;73(1):319-30
references.pmid: 23074284
references.citation: Nanotechnology. 2010 Oct 22;21(42):425102
references.pmid: 20858930
references.citation: J Biomol Screen. 2007 Oct;12(7):925-37
references.pmid: 17942785
references.citation: PLoS One. 2012;7(9):e44640
references.pmid: 22970274
references.citation: Biochim Biophys Acta. 1986 May 9;857(1):123-6
references.pmid: 3964703
references.citation: Nat Clin Pract Oncol. 2007 Feb;4(2):86-100
references.pmid: 17259930
references.citation: Appl Phys Lett. 2011 May 9;98(19):193702
references.pmid: 21915155
references.citation: Free Radic Biol Med. 2013 Jul;60:201-10
references.pmid: 23459071