Polymeric micelles for apoptosis-targeted optical imaging of cancer and intraoperative surgical guidance.

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.
AuthorsHyunah Cho, Clifford S Cho, Guilherme L Indig, Afsaneh Lavasanifar, Mohammad Reza Vakili, Glen S Kwon
JournalPloS one (PLoS One) Vol. 9 Issue 2 Pg. e89968 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24587157 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Fluorescent Dyes
  • Lactones
  • Micelles
  • Veratrum Alkaloids
  • poly(ethylene glycol)-block-poly(epsilon-caprolactone)
  • Polyethylene Glycols
  • Gossypol
  • Paclitaxel
  • cyclopamine
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Apoptosis (drug effects)
  • Female
  • Fluorescent Dyes (administration & dosage, pharmacology)
  • Gossypol (pharmacology)
  • Humans
  • In Situ Nick-End Labeling
  • Injections, Intraperitoneal
  • Lactones (administration & dosage)
  • Luminescent Measurements
  • Mice
  • Micelles
  • Neoadjuvant Therapy (methods)
  • Optical Imaging (methods)
  • Ovarian Neoplasms (drug therapy, pathology, surgery)
  • Paclitaxel (pharmacology)
  • Polyethylene Glycols (administration & dosage)
  • Surgery, Computer-Assisted (methods)
  • Veratrum Alkaloids (pharmacology)

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