Controlled and targeted tumor chemotherapy by ultrasound-activated nanoemulsions/microbubbles.
The paper reports the results of nanotherapy of ovarian, breast, and pancreatic cancerous tumors by paclitaxel-loaded nanoemulsions that convert into microbubbles locally in tumor tissue under the action of tumor-directed therapeutic ultrasound. Tumor accumulation of nanoemulsions was confirmed by ultrasound imaging. Dramatic regression of ovarian, breast, and orthotopic pancreatic tumors was observed in tumor therapy through systemic injections of drug-loaded nanoemulsions combined with therapeutic ultrasound, signifying efficient ultrasound-triggered drug release from tumor-accumulated nanodroplets. The mechanism of drug release in the process of droplet-to-bubble conversion is discussed. No therapeutic effect from the nanodroplet/ultrasound combination was observed without the drug, indicating that therapeutic effect was caused by the ultrasound-enhanced chemotherapeutic action of the tumor-targeted drug, rather than the mechanical or thermal action of ultrasound itself. Tumor recurrence was observed after the completion of the first treatment round; a second treatment round with the same regimen proved less effective, suggesting that drug-resistant cells were either developed or selected during the first treatment round.
Rapoport
Natalya Y
NY
Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA. natasha.rapoport@utah.edu
Kennedy
Anne M
AM
Shea
Jill E
JE
Scaife
Courtney L
CL
Nam
Kweon-Ho
KH
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D051379:Mice; D045423:Microbubbles; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D044367:Phase Transition; D014465:Ultrasonics
D004655:Emulsions; D017239:Paclitaxel