title: Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy.
abstract: For development of tumor-specific chemotherapy, we designed liposomes with temperature-triggered drug release and magnetic resonance imaging (MRI) functions. We prepared multi-functional liposomes by incorporating thermosensitive poly(2-ethoxy(ethoxyethyl)vinyl ether) chains with a lower critical solution temperatures around 40 °C and polyamidoamine G3 dendron-based lipids having Gd(3+) chelate residues into pegylated liposomes. These stable doxorubicin (DOX)-loaded liposomes retained DOX in their interior below physiological temperature but released DOX immediately at temperatures greater than 40 °C. They exhibited excellent ability to shorten the longitudinal proton relaxation time. When administered intravenously into colon 26 tumor-bearing mice, accumulated liposomes in tumors increased with time, reaching a constant level 8 h after administration by following T(1)-weighted MRI signal intensity in tumors. Liposome size affected the liposome accumulation efficiency in tumors: liposomes of about 100 nm diameter were accumulated more efficiently than those with about 50 nm diameter. Tumor size also affected accumulation: more efficient accumulation occurred in larger tumors. Tumor growth was strongly suppressed when liposomes loaded with DOX were administered intravenously into tumor-bearing mice and the tumor was heated mildly at 44 °C for 10 min at 8 h after administration. Multi-functional liposomes having temperature-triggered drug release and MRI functions might engender personalized chemotherapy, providing efficient patient-optimized chemotherapy.
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Naka-ku, Sakai, Osaka, Japan. kono@chem.osakafu-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Kono
authors.forename: Seiji
authors.initials: S
authors.lastname: Nakashima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kokuryo
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimomoto
authors.forename: Sadahito
authors.initials: S
authors.lastname: Aoshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Maruyama
authors.forename: Eiji
authors.initials: E
authors.lastname: Yuba
authors.forename: Chie
authors.initials: C
authors.lastname: Kojima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Harada
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry*; D005260:Female; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D011108:Polymers; D004317:Doxorubicin