Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells

Ramtin Rahmanzadeh, Prakash Rai, Johannes Gerdes, Tayyaba Hasan

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.
OriginalspracheEnglisch
TitelReporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II
Redakteure/-innenAchilefu Samuel, Raghavachari Ramesh
Seitenumfang5
Band757602
Herausgeber (Verlag)SPIE
Erscheinungsdatum16.02.2010
Seiten757602 EP - 7576-5
ISBN (Print)9780819479723
DOIs
PublikationsstatusVeröffentlicht - 16.02.2010
VeranstaltungSPIE BIOS
- San Francisco, USA / Vereinigte Staaten
Dauer: 23.01.201028.01.2010

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