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.