title: A novel ultrasound-triggered drug vehicle with multimodal imaging functionality.
abstract: A novel remotely triggered drug vehicle having multimodal imaging functionality was developed. It exhibits magnetic resonance (MR) imaging, ultrasound (US) imaging, encapsulation of a hydrophobic agent and US-triggered release behavior. Lipophilic superparamagnetic iron oxide (SPIO) nanoparticles were self-assembled with an amphiphilic chitosan derivative, carboxymethyl hexanoyl chitosan (CHC), to form superparamagnetic CHC/SPIO micelles and then loaded with camptothecin (a hydrophobic anticancer agent). The superparamagnetic micelles were then conjugated with albumin-based microbubbles (MBs) to form superparamagnetic micelle-decorated MBs (CHC/SPIO-decorated MBs). The albumin MBs and CHC/SPIO-decorated MBs both demonstrated in vitro concentration-dependent US imaging contrast. Interestingly, the in vitro US contrast was enhanced by decoration. In vivo US images showed that the B-mode contrast of the proposed vehicles could be clearly observed in the veins and arteries of Sprague-Dawley rats. Moreover, the proposed vehicle exhibited significant US-triggered release behavior under therapeutic US sonication at a frequency of 1MHz and power density of 2.4Wcm(-2) for 30min. However, similar behavior was not observed under diagnostic US bombardment at a frequency of 12MHz and mechanical index of 0.5. On the other hand, in vitro MR images of the CHC/SPIO-micelle-decorated MBs also revealed a significant concentration-dependent T(2) (spin-spin relaxation time) contrast due to their decoration with superparamagnetic micelles. Most importantly, the r(2)(∗)-r(2) value of the CHC/SPIO-decorated MBs decreased after therapeutic US bombardment for 30min. This might be considered as an index to probe destruction of the drug-loaded CHC/SPIO micelles.
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC. andyliudpum@yahoo.com.tw
authors.forename: Tse-Ying
authors.initials: TY
authors.lastname: Liu
authors.forename: Meng-Yu
authors.initials: MY
authors.lastname: Wu
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Lin
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Yang
mesh_terms: D000818:Animals; D002166:Camptothecin / Q000494:pharmacology*; D002417:Cattle; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D045423:Microbubbles; D053758:Nanoparticles / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014465:Ultrasonics / Q000379:methods*; D014961:X-Ray Diffraction
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; C522410:carboxymethyl-hexanoyl chitosan; D012710:Serum Albumin, Bovine; D048271:Chitosan; C065507:ferumoxides; D002166:Camptothecin