This proposal will draw on several institutions within the greater Texas Medical Center consortium, as well as on two biotech startups. The Sister Institutions include The University of Texas M.D. Anderson Cancer Center (UTMDACC), The University of Texas Health Sciences Center Houston/Herrmann Hospital (UTHSCH), The University of Texas Medical Branch Galveston (UTMB), and the commercial enterprises include a UTMB startup, AptaMed, and NanoBioMagnetics, Inc. (NBMI), in Oklahoma City, OK.

This multi-disciplinary collaboration builds on several key areas of expertise and proven concepts. First, colleagues at NBMI have demonstrated that magnetically-responsive nanoparticles (MNPs) can be positioned in selected epithelial tissues as directed by appropriate magnetic fields, in studies of the feasibility of applying MNP technology to hearing remediation. Second, colleagues at UTMB and AptaMed, a UTMB startup, have an outstanding record of success in selecting high-affinity thioaptamers, having demonstrated such ability against a wide spectrum of molecular targets, including cell-surface proteins. Third, at MDACC, we have validated the proteoglycan, CD44, which is over-expressed on several distinct tumor histologies, as a target for paclitaxel prodrugs: a paradigm for the proposed role of MNPs as drug carriers in the current approach.

The specific objectives of this seed proposal include: selection of thioaptamers reacting with the CD44 family; conjugation of the CD44 thioaptamer to MNPs, as well as coupling paclitaxel to the MNP conjugate; finally, initial evaluation of the in vitro specificity and cytotoxicity of the CD44-targeted aptamer-MNP-paclitaxel prodrug and in vivo evaluation of its acute and long-term toxicity characteristics in rodent hosts that will be the bases for future antitumor efficacy studies.

The latter Aims and such future efficacy studies will form the initial basis for further preclinical development, and if positive results are forthcoming, the path to an IND application.