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WE‐FG‐BRA‐11: Theranostic Platinum Nanoparticle for Radiation Sensitization in Breast Cancer Radiotherapy
Author(s) -
Yue Y,
Wagner S,
MedinaKauwe L,
Cui X,
Zhang G,
Shiao S,
Sandler H,
Fraass B
Publication year - 2016
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.4957911
Subject(s) - confocal microscopy , clonogenic assay , confocal , cancer cell , breast cancer , chemistry , sensitization , cancer research , apoptosis , medicine , cancer , microbiology and biotechnology , biology , biochemistry , immunology , geometry , mathematics
Purpose: We have developed a novel receptor‐targeted theranostic platinum nanoparticle (HER‐PtNP) for enhanced radiation sensitization in HER2‐positive breast cancer radiation treatment. This study aims to evaluate receptor‐targeting specificity, and radiation sensitization of the nanoparticle. Methods: The platinum nanoparticle (PtNP) was synthesized with the diameter of 2nm, and capped with cysteine. The nanoparticle was tagged with a fluorescent dye (cy5) for the fluoresence detection, and conjuated with HER2/3 targeted protein (HerPBK10) for HER2‐targeting specificity. We evaluated the theranostic features using in vitro breast cancer cell models: HER2‐positive BT‐474, and HER2‐negative MDA‐MB‐231. The HER2‐targeting specificity was evaluated using immunofluorescence and confocal microscopy. For each cell line, three sets of samples, including non‐stained control, fluorescence stained PtNP‐cy5 treated, and HER‐PtNP treated, were imaged by confocal microscopy. Two breast cancer cell lineages were incubated with PtNP and HER‐PtNP at 10 µg/mL, and then irradiated with X‐rays for 2 Gy dose at 50 kVp. A colonogenic assay was used to determine cellular survival fractions by immediately reseeding 300 cells after irradiation in growth media and allowing colonies to grow for 2 weeks. Results: The results of confocal images show that no apparent nanoparticle cellular uptake was observed in the HER2‐(MDA‐MB‐231) cells with 1% for PtNP‐cy5 and 0.5% for HER‐PtNP. Similarly no apparent PtNP‐cy5 uptake (<1%) for BT474 cells was observed. However, there was significant HER‐PtNP uptake (73%) for the HER2+(BT474) cells. The clonogenic assay showed that BT474 cells treated with HER‐PtNP had significantly lower survival compared to those treated with PtNP (32% vs 81%, p=0.01). However, no significant radiosensitivity enhancement was observed for MDA‐MB‐231 cell treated with PtNP and HER‐PtNP (89% vs 92%, p=0.78). Conclusion: Our studies suggest that the HER2‐targeted platinum nanoparticle has excellent receptor targeting specificity and enhanced radiation sensitization compared to nanoparticle alone, suggesting potential for clinical applications in breast cancer radiotherapy.