title: Targeted temperature sensitive magnetic liposomes for thermo-chemotherapy.
abstract: We describe folate receptor targeted thermosensitive magnetic liposomes, which are designed to combine features of biological and physical (magnetic) drug targeting for use in magnetic hyperthermia-triggered drug release. The optimized liposome formulation DPPC:cholesterol:DSPE-PEG(2000):DSPE-PEG(2000)-Folate at 80:20:4.5:0.5 molar ratio showed calcein release of about 70% both in PBS and in 50% FBS (fetal bovine serum) at 43 degrees C and less than 5% release at 37 degrees C following 1h incubation. Folate-targeted doxorubicin-containing magnetic liposomes of the above lipid composition (MagFolDox) showed encapsulation efficiencies of about 85% and 24% for doxorubicin and magnetic nanoparticles (mean crystallite size 10nm), respectively. This magnetic formulation displayed the desired temperature sensitivity with 52% doxorubicin release in 50% fetal bovine serum (FBS) following 1h incubation at 43 degrees C. MagFolDox, when physically targeted to tumor cells in culture by a permanent magnetic field yielded a substantial increase in cellular uptake of doxorubicin as compared to Caelyx (a commercially available liposomal doxorubicin preparation), non-magnetic folate-targeted liposomes (FolDox) and free doxorubicin in folate receptor expressing tumor cell lines (KB and HeLa cells). This resulted in a parallel increase in cytotoxicity over Caelyx and FolDox. Magnetic hyperthermia at 42.5 degrees C and 43.5 degrees C synergistically increased the cytotoxicity of MagFolDox. The results suggest that an integrated concept of biological and physical drug targeting, triggered drug release and hyperthermia based on magnetic field influence can be used advantageously for thermo-chemotherapy of cancers.
authors.affiliation: School of Biosciences and Bioengineering, IIT Bombay, Mumbai, India.
authors.forename: Pallab
authors.initials: P
authors.lastname: Pradhan
authors.forename: Jyotsnendu
authors.initials: J
authors.lastname: Giri
authors.forename: Finn
authors.initials: F
authors.lastname: Rieken
authors.forename: Christian
authors.initials: C
authors.lastname: Koch
authors.forename: Olga
authors.initials: O
authors.lastname: Mykhaylyk
authors.forename: Markus
authors.initials: M
authors.lastname: Döblinger
authors.forename: Rinti
authors.initials: R
authors.lastname: Banerjee
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Bahadur
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D058973:Folate Receptors, GPI-Anchored; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008280:Magnetics; D009369:Neoplasms / Q000188:drug therapy; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013696:Temperature
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D004317:Doxorubicin