Program Information
Tumor-Targeted Peptide-Conjugated Nanoparticle for Radiation Sensitization in Breast Cancer Radiotherapy
Y Yue*, S Wagner , Y Zhang , G Zhang , L Median-Kauwe , H Sandler , B Fraass , Cedars-Sinai Medical Center, Los Angeles, CA
Presentations
MO-DE-605-10 (Monday, July 31, 2017) 1:45 PM - 3:45 PM Room: 605
Purpose: Triple-negative breast cancer (TNBC), defined by negative ER, PR and HER2 markers, is aggressive disease with poor survival. We have developed a novel receptor-targeted peptide-conjugated platinum nanoparticle FPR-PtNP for enhanced radiation sensitization in TNBC radiation treatment. This study evaluates tumor-targeting specificity and radio-sensitization of the new nanoparticle.
Methods: The platinum nanoparticle (PtNP) was synthesized with 2nm diameter, and capped with cysteine. The nanoparticle was conjugated with a protein-coupled peptide, FPR, with TNBC receptor-targeting specificity. To monitor uptake, the nanoparticle was labelled with fluorescent dye(cyanine-7) for optical imaging. We evaluated theranostic properties using in vitro breast cancer cell models BT-474(HER2+) and MDA-MB-231(TNBC). Tumor targeting specificity was evaluated using in vitro immunofluorescence microscopy and optical imaging on the MDA-MB-231 xenograft model. Radiosensitivity was evaluated by incubating cancer cells with FPR-PtNP (1.5μg/mL, 2hr) followed by irradiation (50 kVp xrays, 2 Gy). DNA damage was evaluated by a gamma-H2AX assay. A colonogenic assay determined cellular survival fractions by immediately reseeding 500 cells after irradiation and allowing colonies to grow for 2 weeks.
Results: Immunofluorescence images show strong nanoparticle uptake in TNBC cells(MDA-MB-231), but no apparent uptake for HER2+ cells. Significant tumor uptake was observed in MDA-MD-231 xenograft mice. The gamma-H2AX assays show a significant 43.5% increase of DNA double-strand breaks for TNBC cells treated with FPR-PtNP/irradiation compared to those treated with non-targeting PtNP/irradiation. No targeting-associated enhancement was observed for HER2+ cells. Clonogenic assays showed MDA-MD-231 cells treated with FPR-PtNP had significantly lower survival compared to those treated with PtNP (39% vs 79%, p=0.032). However, no apparent radiosensitivity enhancement was observed for HER2+ cells treated with PtNP and FPR-PtNP (74% vs 69%, p=0.705).
Conclusion: The newly developed peptide nanoparticle FPR-PtNP shows superior targeting selective specificity, fluorescence imaging compatibility and enhanced radiation sensitization, suggesting potential clinical applications toward specific personalized treatment for TNBC patients.
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