3D collagen-based scaffolds as gene delivery platforms for the treatment of human breast cancer

Gene therapy has recently become a potential method for the targeted treatment of cancer but successful delivery remains a real problem that hinders its use in the clinic. The aim of this study is to create and define three-dimensional (3D) lab-based models of breast cancer to mimic primary and secondary tumours, and to assess the ability of these models, when combined with gene delivery using nano-sized particles, as effective anticancer platforms. Traditionally, cancer cell growth has been performed on 2D tissue culture plastic but it lacks the shape found within the tumour environment thus not providing an adequate 3D representation. The alternative involves the use of tumour development in animal models but also has various associated limitations. Recently, 3D lab cell growth has been proposed to bridge the gap in cancer research between conventional 2D cell growth and animal model tumours by enabling cells to acquire properties and respond naturally to the tumour environment. Scaffolds made of natural materials such as collagen, are capable of supporting cell culture and have been widely used as gene delivery platforms for tissue engineering and regenerative medicine within our laboratory. Features include a 3D structure with high compatibility for cell growth making them capable of mimicking the tumour environment. Early work by the applicant has demonstrated successful gene delivery using nanoparticles in a 3D collagen-nanohydroxyapatite (coll-nHA) scaffold mimicking prostate cancer bone metastasis. We believe that collagen scaffolds may be used as 3D lab "tumours" that mimic characteristics of primary tumour progression while coll-nHA scaffolds may serve as templates for the study of secondary cancer tumours in bone (bone metastasis) as it is believed hydroxyapatite may be involved in metastasis pathogenesis. Furthermore, these gene delivery scaffold-based models may be used for the development of new treatment targets for a range of cancer types.

Award Date: 27 June 2019
Award Value: €369,954.52
Principal Investigator: Dr Caroline Curtin
Host Institution: Royal College of Surgeons in Ireland
Scheme: Investigator Led Projects