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Proceedings Paper

Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells
Author(s): Ramtin Rahmanzadeh; Prakash Rai; Johannes Gerdes; Tayyaba Hasan
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Paper Abstract

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.

Paper Details

Date Published: 16 February 2010
PDF: 5 pages
Proc. SPIE 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II, 757602 (16 February 2010); doi: 10.1117/12.843850
Show Author Affiliations
Ramtin Rahmanzadeh, Wellman Ctr. for Photomedicine (United States)
Prakash Rai, Wellman Ctr. for Photomedicine (United States)
Johannes Gerdes, Research Ctr. Borstel (Germany)
Tayyaba Hasan, Wellman Ctr. for Photomedicine (United States)

Published in SPIE Proceedings Vol. 7576:
Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II
Samuel Achilefu; Ramesh Raghavachari, Editor(s)

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