title: Microwave-Triggered Smart Drug Release from Liposomes Co-encapsulating Doxorubicin and Salt for Local Combined Hyperthermia and Chemotherapy of Cancer.
abstract: The microwave and temperature sensitive liposomes were fabricated successfully from 1,2-dipalmityol-sn-glycero-3-phosphocholine (DPPC), cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 (DSPE-PEG2000) with a molar ratio of 4:1:0.26 by co-encapsulating NaCl and doxorubicin (DOX) through the thin-film hydration method to externally manipulate drug release at a predetermined location in the body at a desired time in the right dosage for combination microwave hyperthermia and chemotherapy of cancer to afford a synergistic therapeutic effect. It was found that the confinement of the high concentration of NaCl ions inside the small size of the liposomes led to a more-rapid temperature elevation than the dissociative ions upon microwave treatment. More than 67.6% doxorubicin was released from the DOX and NaCl co-loaded liposomes (DOX&NaCl@liposomes) upon microwave irradiation for 2 min. After incubation with 2 mg/mL DOX&NaCl@liposomes for 4 h followed by treatment with microwave for 2 min, the inhibition rate of human breast cancer cell MDA-MB-231 was evaluated as 76.1%, much higher than that for NaCl@liposomes (29.8%) and DOX@liposomes (40.2%). The tumor growth inhibition was evaluated to be 73.4% after intravenous injection of DOX&NaCl@liposomes followed by microwave irradiation, much higher than that with only NaCl@liposomes (41.5%) or DOX@liposomes (45.5%) combined with microwave irradiation. Therefore, DOX&NaCl@liposomes could serve as a promising thermochemotherapy nanomedicine for cancer treatment because of its excellent microwave susceptible property and good biocompatibility.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
authors.forename: Yushen
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
authors.forename: Yunkun
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Biomedical Engineering, College of Engineering, Peking University , Beijing 100871, China.
authors.forename: Zhifei
authors.identifier: http://orcid.org/0000-0002-6724-0549
authors.initials: Z
authors.lastname: Dai
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000628:therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D065546:Drug Liberation; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008872:Microwaves; D012965:Sodium Chloride / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D012965:Sodium Chloride; D004317:Doxorubicin