title: Polymeric micelles for apoptosis-targeted optical imaging of cancer and intraoperative surgical guidance.
abstract: In a two-step strategy, an intraperitoneal (IP) injection of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles containing paclitaxel (PTX), cyclopamine (CYP), and gossypol (GSP) at 30, 30, and 30 mg/kg, respectively, debulked tumor tissues by 1.3-fold, based on loss of bioluminescence with <10% body weight change, and induced apoptosis in peritoneal tumors when used as neoadjuvant chemotherapy (NACT) in an ES-2-luc-bearing xenograft model for ovarian cancer. In a second step, a single intravenous (i.v.) injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a near-infrared (NIR) fluorescence probe, DiR (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide), resulted in increased peritoneal DiR accumulation in apoptosis-induced ES-2-luc tumor tissues (ex vivo) by 1.5-fold compared with DiR molecules delivered by methoxy PEG-b-PCL micelles (non-targeted) at 48 h after i.v. injection in a second step. As a result, a tandem of PEG-b-PCL micelles enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI) of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence imaging of therapy-induced apoptosis for intraoperative surgical guidance may be a promising treatment strategy for metastatic ovarian cancer.
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Hyunah
authors.initials: H
authors.lastname: Cho
authors.affiliation: Section of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Clifford S
authors.initials: CS
authors.lastname: Cho
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin, Milwaukee, Wisconsin, Unites States of America.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Indig
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Lavasanifar
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Vakili
authors.affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000494:pharmacology; D006072:Gossypol / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007783:Lactones / Q000008:administration & dosage*; D008163:Luminescent Measurements; D051379:Mice; D008823:Micelles; D020360:Neoadjuvant Therapy / Q000379:methods; D061848:Optical Imaging / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017239:Paclitaxel / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D007783:Lactones; D008823:Micelles; D014704:Veratrum Alkaloids; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; D006072:Gossypol; D017239:Paclitaxel; C000541:cyclopamine