title: MRI Monitoring of Tumor-Selective Anticancer Drug Delivery with Stable Thermosensitive Liposomes Triggered by High-Intensity Focused Ultrasound.
abstract: Monitoring of drug release from a heat-activated liposome carrier provides an opportunity for real-time control of drug delivery and allows prediction of the therapeutic effect. We have developed short-chain elastin-like polypeptide-incorporating thermosensitive liposomes (STLs). Here, we report the development of STL encapsulating gadobenate dimeglumine (Gd-BOPTA), a MRI contrast agent, and doxorubicin (Dox) (Gd-Dox-STL). The Dox release profile from Gd-Dox-STL was comparable to Gd-Dox-LTSL; however, the serum stability of Gd-Dox-STL was much higher than Gd-Dox-LTSL. MRI studies showed that the difference in T1 relaxation time between 37 and 42 °C for Gd-Dox-STL was larger than the difference for Gd-Dox-LTSL. Although relaxivity for both liposomes at 42 °C was similar, the relaxivity of Gd-Dox-STL at 37 °C was 2.5-fold lower than that of Gd-Dox-LTSL. This was likely due to Gd-BOPTA leakage from the LTSL because of low stability at 37 °C. Pharmacokinetic studies showed plasma half-lives of 4.85 and 1.95 h for Gd-Dox-STL and Gd-Dox-LTSL, respectively, consistent with in vitro stability data. In vivo MRI experiments demonstrated corelease of Dox and Gd-BOPTA from STL under mild hyperthermia induced by high-intensity focused ultrasound (HIFU), which suggests STL is a promising tumor selective formulation when coupled with MR-guided HIFU.
authors.affiliation: Bio Therapeutics Laboratory, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd. , #130, Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Hyun Ryoung
authors.initials: HR
authors.lastname: Kim
authors.forename: Dong Gil
authors.initials: DG
authors.lastname: You
authors.affiliation: Bio Therapeutics Laboratory, Samsung Advanced Institute of Technology (SAIT), Samsung Electronics Co., Ltd. , #130, Samsung-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 443-803, South Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyu-Sil
authors.initials: KS
authors.lastname: Choi
authors.forename: Wooram
authors.initials: W
authors.lastname: Um
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.forename: Young-Sun
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation / Q000502:physiology; D004549:Elastin / Q000008:administration & dosage; D006207:Half-Life; D006358:Hot Temperature; D006979:Hyperthermia, Induced / Q000379:methods; D008081:Liposomes / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics; D010455:Peptides / Q000008:administration & dosage; D013696:Temperature; D014463:Ultrasonography / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D008081:Liposomes; D009942:Organometallic Compounds; D010455:Peptides; C064572:gadobenic acid; D008536:Meglumine; D004317:Doxorubicin; D004549:Elastin
keywords: MRI; drug release monitoring; elastin-like polypeptide; heat-triggered drug release; intratumoral accumulation; thermosensitive liposome