title: Effective tumor treatment using optimized ultrasound-mediated delivery of bleomycin.
abstract: Bleomycin is a nonpermeant, hydrophilic macromolecule with a high intrinsic anticancer cytotoxicity. However, the cytotoxic potential of the drug is restricted by its low membrane permeability. Application of low-intensity ultrasound to growing tumors enhances intracellular delivery of bleomycin after IP or intratumoral administration, thereby potentiating its cytotoxicity. Optimization of ultrasound parameters for in-vivo bleomycin delivery was undertaken, and an effective antitumor effect was demonstrated in solid tumors of both murine and human cell lines. Cell death after treatment was shown to occur by an apoptotic mechanism. The results achieved in these experiments were equivalent to those achieved using electroporation to mediate delivery of bleomycin-electrochemotherapy. We found that, although temperature rises of up to 5 degrees C occur using the optimized ultrasound conditions, this effect is not responsible for the potentiated drug cytotoxicity. This technique could be used with focused ultrasound or with endoscopic ultrasound probes to develop a localized and effective anticancer treatment with little or no systemic toxicity. (E-mail: Geraldc@ccrc.ie).
authors.affiliation: Cork Cancer Research Centre, Leslie C. Quick Laboratory, University College Cork, Cork, Ireland.
authors.forename: John O
authors.initials: JO
authors.lastname: Larkin
authors.forename: Garrett D
authors.initials: GD
authors.lastname: Casey
authors.forename: Mark
authors.initials: M
authors.lastname: Tangney
authors.forename: James
authors.initials: J
authors.lastname: Cashman
authors.forename: Chris G
authors.initials: CG
authors.lastname: Collins
authors.forename: Declan M
authors.initials: DM
authors.lastname: Soden
authors.forename: Gerald C
authors.initials: GC
authors.lastname: O'Sullivan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001761:Bleomycin / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D009369:Neoplasms / Q000188:drug therapy*; D015612:Phonophoresis / Q000379:methods*; D013194:Staining and Labeling
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin