(EGF-Au NPs) provide an efficient nano

LB120
Theme: Radiotherapy and radiobiology
EGF-coated gold nanoparticles (EGF-Au NPs) provide an efficient nano-scale delivery
approach to the molecular radiotherapy of EGFR-positive cancer
Lei Song (1), Sarah Able (1), Phoebe Lam (1), Christopher Hillyar (1), Georgina Royle (1),
Katherine Vallis (1) presenting
CRUK/MRC Oxford Institute for Radiation Oncology, Oxford, UK (1)
Background
Radiolabelled antibodies and peptides hold promise for molecular radiotherapy but are often limited
by low payload resulting in inadequate radioactivity delivery to tumour tissue and, therefore, modest
therapeutic effect. Adverse effects may occur when significant amounts of the administered
radioactivity accumulates in and irradiates normal tissue. Nanomedicines that incorporate targeting
ligands can selectively deliver therapeutic agents to malignant cells and exploit the multivalency
principle to maximise binding affinity, resulting in enhanced targeting and therapeutic efficacy with few
side effects. We have developed a straightforward and effective synthetic method for 111In-labelled
EGF-gold nanoparticles (111In-EGF-Au NPs) for molecular radiotherapy.
Method
DTPA-coupled EGF and gold NPs were mixed, and subsequently linked via interaction between gold
and the disulfide bonds of EGF. EGF-Au NPs were purified by centrifugation, and radiolabelled using
111InCl3. Human breast cancer cell lines (MDA-MB-468 which overexpresses EGFR and MCF-7, a
negative control) were exposed to 111In-EGF-Au for 4 hr. The targeting efficiency of 111In-EGF-Au
was investigated by counting internalised radioactivity and by confocal imaging following exposure of
cells to Cy3-modified EGF-Au. Cytotoxicity was evaluated in clonogenic assays.
Results
Cellular internalisation assays showed that the proportion of radioactivity internalised by MDA-MB-468
and MCF7 cells was 15% and 1.3% respectively (using a mixing ratio of Au:EGF of 1:160; [EGF]=40
nM; specific activity=6MBq/µg). This indicates 111In-EGF-Au NPs selectively target EGFR-positive
cells via EGF/EGFR binding resulting in high 111In uptake. This was visualised and confirmed using
confocal microscopy that showed immunofluorescence in MDA-MB-468 cells but not MCF-7 following
exposure to Cy3-EGF-Au. In clonogenic assays,111In-EGF-Au were radiotoxic to MDA-MB-468 but
not MCF7 cells with a surviving fraction of 17.1 ± 4.4% versus 89.8 ± 1.4% (P<0.001) after exposure
for 4hr (Au:EGF 1:160).
Conclusion
In conclusion, a simple synthetic process for an 111In-labelled EGF-Au nanosystem was developed.
EGF-Au NPs enable targeted delivery of 111In specifically to EGFR-positive cancer cells.

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