Intracellular Protein Delivery for Treating Breast Cancer
Annual rept. 15 May 2011-14 May 2012
UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
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The development of stimuli-responsive, nano-scale therapeutics that can selectively target tumors is a major research focus in cancer nanotechnology. A potent therapeutic option is directly arming the cancer cells with apoptotic-inducing proteins that are not targeted by anti-apoptotic maneuvers found in tumors. The avian virus derived apoptin forms a high molecular weight protein complex that selectively accumulates in the nuclei of cancer cells to induce apoptotic cell death. To enable the efficient delivery of this tumor-selective complex in functional form, we synthesized degradable, sub-100 nm, core-shell protein nanocapsules containing the 2.4 MDa apoptin complexes. Recombinant apoptin is reversibly encapsulated in a positively charged, water soluble polymeric shell and is released in native forms in response to reducing conditions such as the cytoplasm. The nanocapsules are efficiently internalized by mammalian cells lines as characterized by confocal microscopy, and rhodamine-labeled apoptin can be observed in the nuclei of cancer cells only. Released apoptin induced tumor-specific apoptosis in several cell lines and inhibited tumor growth in vivo, demonstrating the potential of this polymer-protein combination as a cancer therapeutic.
- Medicine and Medical Research