Previously, as an American Cancer Society Postdoctoral Fellow, I developed the first demonstration of long-circulating bismuth sulfide nanoparticles as contrast agents for receptor targeted breast cancer CT imaging. The high atomic number of bismuth and the density of bismuth sulfide enable a significant X-ray attenuation making the particles visible in CT images. Traditionally, cancer diagnosis using CT is challenging due to the poor resolution of tumors. Using a peptide (LyP-1) ligand coated nanoparticle we were able to demonstrate the first tumor-targeted nanoparticle CT contrast agent. This proposal will build on the initial findings while significantly enhancing the capabilities of the first generation design allowing greater potential utility of this class of materials to be implemented not only in diagnosis at the primary tumor site but also in tracking metastasis. Furthermore, the use of nanoparticle contrast agents enables the possibility of more cutting-edge techniques such as K-edge, and multi-contrast CT imaging, in addition to targeting disease phenotypes through ligand coated nanoparticle and cell/tissue interactions.
Current oncology research requires the use of time-consuming, and expensive, mouse models such as genetically engineered mice (GEMMs) or severely compromised immunodeficient (SCID) mice that are hosts to transplanted human tumour cells. There are several additional drawbacks to using these models including (i) SCID mice lose their lymphocyte-mediated tumour response thus altering the tumour microenvironment, (ii) GEMM mice have limited numbers of gene targets possible making genetically heterogeneous models incredibly challenging, (iii) GEMM tumour development is variable and can take years to form, (iv) both models involve animal research requiring costs, space requirements, and ethical concerns. GEMMs while theoretically a better method to model tumour heterogeneities suffer from several drawbacks including how a mouse host is genetically and physiologically different from a human host. This research stream focuses on developing three-dimensionally engineered heterogeneous tumour tissue constructs to be used as an alternative to small animal models in cancer biology, drug discovery, nanomedicine, and diagnostic tool development. Using three-dimensional printed tumour tissues with human cancer cells and a tumour microenvironment that would mimic the specific tissue being modeled can overcome several of the limitations currently faced from animal models. Additionally this type of tool could serve as a bridge from traditional two-dimensional cell culture methods and in vivo methods. Ultimately, three-dimensionally printed models of complex tumour tissues can be further integrated into higher order devices for organ-(or body)-on-a-chip applications and provide substantial improvements to both mouse models and traditional cell culture methods currently used in medical research