Development of Innovative Nano Dual Drug/Gene Delivery and Biometric 3D Printed Bone Model Platforms for Metastatic Breast Cancer Treatment and Analysis (Synergy)

Submitted by Robert Siegel, M.D., Lijie Grace Zhang, Ph.D., Joseph O’Brien, M.D.
April 28, 2014

Abstract: 

This proposal aims to design a very novel delivery system involving rosette nanotubes (self-assembling guanine-cytosine dimers) covalently linked to a microRNA to target breast cancer cells, and within the nanotube will be a cytotoxic drug such as paclitaxel or tamoxifen. Also linked to the nanotube will be an RGD peptide motif that will act as a directing beacon to tumor cells that typically have up-regulated cell surface proteins that bind the RGD motif (i.e. integrins and CD44). The clinical relevance is obvious: i) targeted delivery to cancer cells (although this reviewer believes that other cells will likewise be targeted by the RGD domain), ii) delivery of a microRNA that can be specific to breast cancer progression/biology, and iii) the ability to more efficiently deliver very hydrophobic molecules such as paclitaxel or tamoxifen.  The PI’s also propose to generate a biometric nano bone scaffolding matrix, using a 3D printer, for testing the ability of their nanotube delivery system to inhibit breast cancer cell metastasis to the biometric material -- in essence they will develop an in vitro model of bone metastasis.

Submitted By:

Robert Siegel, M.D.

Lijie Grace Zhang, Ph.D.

Joseph O'Brien, M.D.