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

doi:10.1117/12.843850

16 February 2010 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

Author Affiliations +

Proceedings Volume 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II; 757602 (2010) https://doi.org/10.1117/12.843850
Event: SPIE BiOS, 2010, San Francisco, California, United States

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.

Citation Download Citation

Ramtin Rahmanzadeh, Prakash Rai, Johannes Gerdes, and Tayyaba Hasan "Targeted light-inactivation of the Ki-67 protein using theranostic liposomes leads to death of proliferating cells", Proc. SPIE 7576, Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications II, 757602 (16 February 2010); https://doi.org/10.1117/12.843850

Access the abstract

PROCEEDINGS
5 PAGES

DOWNLOAD PAPER SAVE TO MY LIBRARY

GET CITATION

CITATIONS

Cited by 1 scholarly publication.

Explore citations on Lens.org

RIGHTS & PERMISSIONS

Get copyright permission Get copyright permission on Copyright Marketplace

KEYWORDS

Proteins

Cancer

Photodynamic therapy

Ovarian cancer

Cell death

Lung

Confocal microscopy

Show All Keywords

RELATED CONTENT

Overcoming chemoresistance using tumor mitochondria-targeted photodynamic therapy
Proceedings of SPIE (February 28 2019)

Dormant cancer cells accumulate high protoporphyrin IX levels and are...
Proceedings of SPIE (August 07 2019)

Effect of the prosurvival protein MCL 1 on photodynamic therapy...
Proceedings of SPIE (March 06 2009)

Nanotechnology-based combination therapy improves treatment response in cancer models
Proceedings of SPIE (July 13 2009)

Involvement of BimL activation in apoptosis induced by lysosomal photodamage
Proceedings of SPIE (March 06 2009)

Improvement of anti tumor activity of photodynamic therapy through inhibition...
Proceedings of SPIE (July 13 2009)

Autophagy in response to photodynamic therapy cell survival vs....
Proceedings of SPIE (February 18 2009)

Subscribe to Digital Library

Receive Erratum Email Alert

Show All Keywords

Keywords/Phrases

Search In:

Publication Years