Gene therapy, encompassing plasmid DNA, microRNA and siRNA delivery, has emerged as a potential therapeutic for cancer treatment as genes can be released locally for a defined timeframe. However, effective gene delivery to abrogate tumour growth remains a crucial barrier to its clinical application. The aim of this study is to develop and characterise 3D in vitro culture models of breast cancer to simulate the primary tumour and secondary cancer bone metastasis, and to use the models to determine the efficacy of nanoparticle-mediated gene delivery as competent anticancer platforms. Culturing of cancer cells in 2D has traditionally been used to study complex tumorigenic mechanisms but lacks the structural microenvironment required for cell-cell and cell-extracellular matrix interactions. The alternative involves animal xenograft models but also has various limitations. Recently, 3D cancer cell culturing has been proposed to bridge the gap between conventional 2D culture and in vivo tumours by enabling cells to acquire phenotypes and respond to stimuli similar to in vivo biological systems. Collagen-based scaffolds capable of supporting cell culture have been widely used as gene delivery platforms for tissue engineering and regenerative medicine within our laboratory. Features include excellent biocompatibility and a 3D structure capable of recapitulating the native tumour geometry demonstrating their potential as extracellular matrix models due to their biomimicry. Preliminary work by the applicant has already demonstrated successful nanoparticle-mediated siRNA delivery in 3D collagen-nanohydroxyapatite scaffolds simulating prostate cancer bone metastasis. We hypothesise that collagen scaffolds may be used as 3D in vitro “tumours” that mimic characteristics of in vivo primary tumour progression while collagen-nanohydroxyapatite scaffolds may serve as bone templates for the study of metastasis as the bone component, hydroxyapatite, may be involved in metastasis pathogenesis. Furthermore, these gene delivery scaffold-based models may serve as excellent tools for the development of novel treatment targets.
