Primary bone cancer scaffolds as controlled release non-viral gene delivery platforms

Objective

Primary bone cancers are aggressive malignancies that characteristically arise during childhood/adolescence. Current treatment involves a multidimensional approach of surgery and chemotherapy but response to therapy can be poor-about 30% of primary bone cancer patients die within 5 years. Despite treatment with various chemotherapy regimens in the past 20 years, survival rates have not improved and no efficacious targeted therapies have been developed. Bone tumours also often colonise large expanses of bone making it difficult to repair itself, thus resulting in a deleterious effect on patient life quality. Therefore, aligning bone tumour therapy and bone regeneration are highly challenging in the clinic. Building on my experience in this area, I propose a frontier technology to progress beyond state-of-the-art; PANACEA describes the engineering of a novel bi-functional biomaterial platform as a new strategy for bone tumour therapy. PANACEA will conquer the issues of current biomaterials approaches by utilising advances in bone tissue engineering to promote more timely bone production. A collagen nanohydroxyapatite based scaffold containing reduced graphene oxide will be developed with pore architecture, mechanical properties and bioactive composition tailored to regenerate bone. Importantly, reduced graphene oxide is suitable for photothermal treatment of cancer cells and promotes bone repair. Utilising the expertise of the applicant on internationally recognised innovative research on scaffold-mediated gene delivery, this system will be further functionalised for the controlled ultrasonic on-demand non-viral delivery of microRNAs to ablate cancer cell growth and direct host stem cells to regenerate stable bone at the tumour location in a timely manner. The proposed PANACEA platform is a groundbreaking exemplar disruptive technology that will revolutionise bone tumour therapy using minimally-invasive therapeutic strategies.