title: Thermosensitive, near-infrared-labeled nanoparticles for topotecan delivery to tumors.
abstract: Liposomal nanoparticles have proven to be versatile systems for drug delivery. However, the progress in clinic has been slower and less efficient than expected. This suggests a need for further development using carefully designed chemical components to improve usefulness under clinical conditions and maximize therapeutic effect. For cancer chemotherapy, PEGylated liposomes were the first nanomedicine to reach the market and have been used clinically for several years. Approaches toward targeted drug delivery using next generation "thermally triggered" nanoparticles are now in clinical trials. However, clinically tested thermosensitive liposomes (TSLs) lack the markers that allow tumor labeling and improved imaging for tissue specific applied hyperthermia. Here we describe the development of optically labeled TSLs for image guidance drug delivery and proof-of-concept results for their application in the treatment of murine xenograft tumors using the anticancer drug topotecan. These labeled TSLs also allow the simultaneous, real-time diagnostic imaging of nanoparticle biodistribution using a near-infrared (NIR; 750-950 nm) fluorophore coupled to a lipidic component of the lipid bilayer. When combined with multispectral fluorescence analysis, this allows for specific and high sensitivity tracking of the nanoparticles in vivo. The application of NIR fluorescence-labeled TSLs could have a transformative effect on future cancer chemotherapy.
authors.affiliation: †Institute of Pharmaceutical Science, King's College London, London, U.K.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Rosca
authors.affiliation: †Institute of Pharmaceutical Science, King's College London, London, U.K.
authors.forename: Michael
authors.initials: M
authors.lastname: Wright
authors.affiliation: †Institute of Pharmaceutical Science, King's College London, London, U.K.
authors.forename: Roman
authors.initials: R
authors.lastname: Gonitel
authors.affiliation: §Department of Experimental Medicine, Imperial College London, London, U.K.
authors.forename: Wladyslaw
authors.initials: W
authors.lastname: Gedroyc
authors.affiliation: †Institute of Pharmaceutical Science, King's College London, London, U.K.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.affiliation: †Institute of Pharmaceutical Science, King's College London, London, U.K.
authors.forename: Maya
authors.initials: M
authors.lastname: Thanou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D019772:Topotecan / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011092:Polyethylene Glycols; D019772:Topotecan
keywords: anticancer; focused ultrasound; multispectral fluorescence imaging; thermosensitive liposomes; topotecan