title: Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery.
abstract: In vivo tumor targeting and drug delivery properties of small polymerized polydiacetylene (PDA) micelles (∼10 nm) is investigated in a murine MDA-MB-231 xenograft model of breast cancer. Three micelles with different surface coatings are synthesized and tested for their ability to passively target tumor through the enhanced permeability and retention effect. After injection (24 h), fluorescence diffuse optical tomographic imaging indicates a tumor uptake of nearly 3% of the injected dose for the micelles with a 2 kDa poly(ethylene glycol) (PEG)-coating (PDA-PEG2000). The uptake of PDA micelles in tumors is confirmed by co-localization with [(18) F]-fluorodeoxyglucose (FDG) positron emission tomography. Although FDG has a higher diffusion rate in tumors, 40 ± 19% of the retained micelles is co-registered with the tumor volume visualized by FDG. Finally, PDA-PEG2000 micelles are loaded with the hydrophobic anticancer drug paclitaxel and used in vivo to inhibit tumor growth. These findings demonstrate the potential of PDA-PEG2000 micelles for both in vivo tumor imaging and drug delivery applications.
authors.affiliation: CEA, I2 BM, Service Hospitalier Frédéric Joliot, INSERM U1023, Laboratoire d'Imagerie Moléculaire Expérimentale, Université Paris Sud, 4 place du général Leclerc, 91401 Orsay, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Mackiewicz
authors.forename: Edmond
authors.initials: E
authors.lastname: Gravel
authors.forename: Anikitos
authors.initials: A
authors.lastname: Garofalakis
authors.forename: Julien
authors.initials: J
authors.lastname: Ogier
authors.forename: Jubi
authors.initials: J
authors.lastname: John
authors.forename: Daniel Miotto
authors.initials: DM
authors.lastname: Dupont
authors.forename: Karine
authors.initials: K
authors.lastname: Gombert
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
authors.forename: Eric
authors.initials: E
authors.lastname: Doris
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ducongé
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D000078789:Polyacetylene Polymer; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D053279:Polyynes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019265:Spectroscopy, Near-Infrared; D014018:Tissue Distribution / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D008823:Micelles; D000078789:Polyacetylene Polymer; D011108:Polymers; D053279:Polyynes; C082361:polydiacetylene; D017239:Paclitaxel