Near-Infrared Nanopolymer Agents for Real-Time, In Vivo Imaging of Tumor Margins

Wei, Jianjun

Abstract

Optical imaging as a noninvasive diagnosis technique is a highly promising tool for real-time, in-vivo detection of tumor margins during breast-conserving surgery. This can decrease false-negative diagnoses and local recurrences of the cancer that occur after conventional diagnoses and lumpectomy. Its clinical application has been held back by lack of suitable imaging agents. There is a clear need to develop imaging agents for extending applications of optical imaging method for real-time breast cancer diagnosis. The challenge of a real- time agent requires deep tissue penetration and visualization, good biocompatibility and stability, as well as capability to distinguish malignant cancer cells from surrounding healthy cells. To address the challenge, we propose to develop novel near-infrared (NIR) nanopolymer agents to real-time identify tumor margins through recognition of molecules that are specifically expressed in tumor cells. A series of tumor-homing peptides for specific binding integrins on cancer cells will be introduced to the polymer agent and tested for optimizing tumor-binding specificity. Our concept is based on an intrinsic NIR-fluorescent conjugated polymer backbone which features: a) high intensity and photostability, b) deep tissue penetration, c) specific sensitivity to tumor cells, d) biocompatibility and e) low cost production. An already established conjugated polymer synthetic route, incorporating chemical and optical characterization, NIR fluorescent imaging will be the starting point for the synergistic effort. Building on our significant preliminary results, the Phase I research will first synthesize the designed agent by incorporating multi-NIR fluorophores and high-density biocompatible side-chains to the conjugated polymer backbone, while the binding peptide will be covalently linked to the side chain. Secondly, we will demonstrate the feasibility of imaging-detection of tumor cells and small clusters of tumor cells (1 mm) within a larger population of cells as proof-of-concept. Phase II efforts will focus on further development of the nanopolymer agent, and deliver mature protocols for synthesis of the NIR imaging agent. We will validate the real-time imaging of breast tumor margin of our nanopolymer agents in animal model imaging using a non-invasive optical imaging system (IVIS 50 fro Xenogen). The success of Phase II will provide a list of optical imaging agents suitable for real-time identification of breast cancer margins. The agents will be primarily marketed to pharmaceutical companies for FDA approval and clinical testing. ? ? ?