title: Non-invasive tumor detection in small animals using novel functional Pluronic nanomicelles conjugated with anti-mesothelin antibody.
abstract: In this study QDs were encapsulated in carboxylated PluronicF127 (F127COOH) triblock polymeric micelles and conjugated with anti-mesothelin antibody for the purpose of alleviating potential toxicity, enhancing the stability and improving targeting efficiency of CdTe/ZnS quantum dots (QDs) in tumors. The amphiphilic triblock polymer of F127COOH contains hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) units. After encapsulating QDs into carboxylated F127 (F127COOH-QD) micelles, the particles were conjugated with anti-mesothelin antibodies to allow targeting of cancerous areas. The size of the monodispersed spherical QD-containing micelles was determined to be ∼120 nm by dynamic light scattering (DLS). The critical micelle concentration (CMC) was estimated to be 4.7 × 10(-7) M. In an in vitro study, the anti-methoselin antibody conjugated F127COOH (Me-F127COOH-QD) nanomicelles showed negligible cytotoxicity to pancreatic cancer cells (Panc-1). Confocal microscopy demonstrated that the Me-F127COOH-QD nanomicelles were taken up more efficiently by Panc-1 cells, due to antibody mediated targeting. An in vivo imaging study showed that Me-F127COOH-QD nanomicelles accumulated at the pancreatic tumor site 15 min after intravenous injection. In addition, the low in vivo toxicity of the nanomicellar formulation was evaluated by pathological assays. These results suggest that anti-mesothein antibody conjugated carboxylated F127 nanomicelles may serve as a promising nanoscale platform for early human pancreatic cancer detection and targeted drug delivery.
authors.affiliation: The Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, The State University of New York at Buffalo, Buffalo, NY 14260, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Ding
authors.forename: Ken-Tye
authors.initials: KT
authors.lastname: Yong
authors.forename: Wing-Chueng
authors.initials: WC
authors.lastname: Law
authors.forename: Indrajit
authors.initials: I
authors.lastname: Roy
authors.forename: Rui
authors.initials: R
authors.lastname: Hu
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhao
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.forename: Folarin
authors.initials: F
authors.lastname: Erogbogbo
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Bergey
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis; D058851:GPI-Linked Proteins; D006801:Humans; D000090204:Mesothelin; D051379:Mice; D008823:Micelles; D018613:Microscopy, Confocal / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011095:Polyethylenes / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D058851:GPI-Linked Proteins; D008823:Micelles; C000715528:Msln protein, mouse; D053769:Nanocapsules; D011095:Polyethylenes; D011126:Polypropylenes; C078661:UCON 50-HB-5100; D000090204:Mesothelin