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

Cho H, Cho CS, Indig GL, Lavasanifar A, Vakili MR, Kwon GS - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.

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.

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Relative BLI and FLI of ROIs in noninvasive whole-body images of ES-2-luc-bearing mouse in a time-dependent manner (*** <0.001).
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pone-0089968-g005: Relative BLI and FLI of ROIs in noninvasive whole-body images of ES-2-luc-bearing mouse in a time-dependent manner (*** <0.001).

Mentions: From noninvasive bioluminescence imaging, quantitative bioluminescence intensity (BLI) in ROI (region of interest: tumor tissues in the abdomen of animals) is presented longitudinally in Figure 5. Two days after termination of treatment, %BLI in ROI (%change in BLI of ROI starting at 6 h after after an IV injection of apoptosis-targeting PEG-b-PCL micelles carrying DiR) increased rapidly up to ca. 60% but %FLI in ROI decreased to ca. −20% in control mice. In contrast, in the experimental group, %BLI in ROI decreased to ca. −50% but %FLI increased to ca. 20%.


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

Cho H, Cho CS, Indig GL, Lavasanifar A, Vakili MR, Kwon GS - PLoS ONE (2014)

Relative BLI and FLI of ROIs in noninvasive whole-body images of ES-2-luc-bearing mouse in a time-dependent manner (*** <0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935963&req=5

pone-0089968-g005: Relative BLI and FLI of ROIs in noninvasive whole-body images of ES-2-luc-bearing mouse in a time-dependent manner (*** <0.001).
Mentions: From noninvasive bioluminescence imaging, quantitative bioluminescence intensity (BLI) in ROI (region of interest: tumor tissues in the abdomen of animals) is presented longitudinally in Figure 5. Two days after termination of treatment, %BLI in ROI (%change in BLI of ROI starting at 6 h after after an IV injection of apoptosis-targeting PEG-b-PCL micelles carrying DiR) increased rapidly up to ca. 60% but %FLI in ROI decreased to ca. −20% in control mice. In contrast, in the experimental group, %BLI in ROI decreased to ca. −50% but %FLI increased to ca. 20%.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.

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.

Show MeSH
Related in: MedlinePlus