Conference Proceeding

Theranostic gold nanoparticles for paediatric neurosurgical applications in medulloblastoma

Dr. Aaron Tan,
University College London, UK

Dr. Aaron Tan is a researcher based in University College London (UCL) Medical School, and is a visiting scholar at the Biomaterials and Advanced Drug Delivery Laboratory (BioADD) at Stanford University. He graduated with a BSc in Surgical Sciences from UCL in 2011, and was awarded his PhD in Surgery and Bioengineering from UCL in 2014. Dr. Aaron Tan is currently completing the clinical years of his MBBS Medicine degree at UCL Medical School. He has held research collaboration positions at various top institutions including Harvard University, University of Oxford, and Imperial College London. To date, he has authored in excess of 40 PubMed-indexed publications, with papers in high-impact factor journals including ACS Nano, Trends in Biotechnology, Advanced Drug Delivery Reviews, among many others. He has 1090 citations, and a h-index of 16. He is a Guest Editor at Frontiers in Pharmacology, and Nano Reviews and Experiments. He works on the forefront of nanotechnology and regenerative therapeutics as applied to clinical medicine and surgery.

Medulloblastoma is the most common and highest grade primary brain tumour in children. Due to its aggressive nature within the brain tissue as well its tendency to metastasize and spread via the cerebrospinal fluid (CSF), complete and curative surgical resection is virtually impossible, giving it a relatively poor prognosis. Furthermore, the blood-brain-barrier (BBB) prevents many chemotherapeutic agents from reaching the intended site. In order to overcome these issues, we initially conducted exploratory research into using gold nanoparticles (AuNP) with cancer-targeting peptides as a “Trojan horse” to penetrate the BBB to deliver chemotherapeutic agents specifically to the tumour sites within the brain. Both in vitro and in vivo aspects of our study indicated a statistically significant decrease in cancer cells when platinum(IV)-loaded AuNPs were used, compared platinum(IV) alone and AuNPs alone. Furthermore, due to its high photoelectric absorption coefficient, we further discovered a synergistic cancer cell killing effect when radiotherapy was applied to AnNPs carrying a payload of chemotherapeutic drug. Results presented herein show an even higher rate of cell kill when platinum(IV)-loaded AuNPs were exposed to a therapeutic dose of radiation, compared to radiation alone and platinum(IV)-loaded AuNPs alone. Finally, we employed platinum(IV)-loaded AuNPs as computed tomography (CT) contrast agents using spectral diffusion algorithm. It was found that platinum(IV)-loaded AuNPs were able to localise to the tumour sites in both in vitro and in vivo models, with possible implications for it to be used in stereotactic neurosurgery. In conclusion, we have developed a novel multifunctional platform technology that can be used in drug delivery, a radiosensitizer in radiotherapy, and a molecular imaging agent for stereotactic surgery in paediatric medulloblastoma.

Published: 27 April 2017