PROCEEDINGS ARTICLE | February 17, 2010
Proc. SPIE. 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II
KEYWORDS: Nanotechnology, Confocal microscopy, Proteins, Oncology, Photodynamic therapy, Cancer, Macromolecules, Lung, Cell death, Ovarian cancer
Nanomedicine is beginning to impact the treatment of several diseases and current research
efforts include development of integrated nano-constructs (theranostics) which serve as probes
for imaging and therapy in addition to delivering macromolecules intracellularly. In cancer, there
is a vital unmet need for effective alternative treatments with high specificity and low systemic
toxicity. This can be achieved by targeting key molecular markers associated with cancer cells
with reduced effective drug doses. Here, we show an innovative proof-of-principle approach for
efficient killing of proliferating ovarian cancer cells by inactivating a protein associated with cell
proliferation namely, the nuclear Ki-67 protein (pKi-67), using nanotechnology-based
photodynamic therapy (PDT). Antibodies against pKi-67 are widely used as prognostic tools for
tumor diagnosis. In this work, anti pKi-67 antibodies were first conjugated to fluorescein
isothiocyanate (FITC) and then encapsulated inside liposomes. After incubation of OVCAR-5
ovarian cancer cells with these liposomes, confocal microscopy confirmed the localization of the
antibodies to the nucleoli of the cells. Irradiation with a 488 nm laser led to a significant loss of
cell viability. The specificity of this approach for pKi-67 positive cells was demonstrated in
confluent human lung fibroblasts (MRC-5) where only a small population of cells stain positive
for pKi-67 and only minimal cell death was observed. Taken together, our findings suggest that
pKi-67 targeted with nano-platform is an attractive therapeutic target in cancer therapy.
