Intracellular Protein Delivery for Treating Breast Cancer
Final rept. 15 May 2011-14 May 2014
CALIFORNIA UNIV LOS ANGELES
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Encapsulating anticancer protein therapeutics in nanocarriers is an attractive option to minimize active drug destruction and increase local accumulation at disease sites. Tumor specific ligands can further facilitate in targeting the nanocarriers to the tumor cells. Rationally designed non-covalent protein nanocapsules, incorporating copper-free click chemistry moieties, polyethylene glycol PEG units, redox-sensitive crosslinker, and tumor specific targeting ligand, have been synthesized to selectively deliver intracellular protein therapeutics to tumor cells via receptor-mediated endocytosis. These nanocapsules can be conjugated to different targeting ligands of choice, such as anti-Her2 antibody single-chain variable fragment and luteinizing hormone releasing hormone LHRH peptide, which result in specific and efficient accumulation within tumor cells overexpressing corresponding receptors. LHRH-conjugated nanocapsules selectively delivered recombinant p53 and its tumor-selective super variant into targeted tumor cells, which led to reactivation of p53-mediated apoptosis. Our results validate a general approach for targeted protein delivery into tumor cells using cellular-responsive nanocarriers.
- Anatomy and Physiology
- Medicine and Medical Research
- Organic Chemistry