Magneto-Plasmonic, Raman active Nanocapsules for Superior Pediatric Brain Cancer Therapy

Project Information

SUPERBRAIN

Grant agreement ID: 840964

DOI

10.3030/840964

Project closed

EC signature date 30 April 2019

Start date 1 September 2020

End date 31 August 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 224 933,76

EU contribution

€ 224 933,76

Coordinated by

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom

Periodic Reporting for period 1 - SUPERBRAIN (Magneto-Plasmonic, Raman active Nanocapsules for Superior Pediatric Brain Cancer Therapy)

Reporting period: 2020-09-01 to 2022-08-31

Summary of the context and overall objectives of the project

Conventional in vitro screening of anticancer products for novel anticancer therapeutics mainly relied on cytotoxicity assays using established cancer cell lines grown as two-dimensional (2D) cultures. The 2D cell cultures has several merits and has contributed significantly to increasing our knowledge of cancer therapeutics and drug screening. However, 2D cell cultures has many limitations including not capable of mimicking the complexity and heterogeneity of clinical tumors as in vivo in the laboratory settings. The Horizon 2020 Marie Skłodowska-Curie Actions (MSCA) project ‘SUPERBRAIN’ addressed this issue and demonstrated laboratory scale three-dimensional (3D) multicellular cancer cell spheroid platform that closely mimic drug penetration, distribution, and final accumulation in cancer cells as that of the solid tumor in the body. The SUPERBRAIN’s scientific discoveries lead to a platform technology that can truly be used in the clinic, and to be very reproducible, fast, and scalable for brain cancers of paediatric (small children) and adult patients. The novel 3D tumor spheroid bridges the gap between the 2D cultures and animal models. This new research allows replicating the architecture of human tumors and better investigates the pathobiology of human cancer. The advantage of the developed 3D tumor spheroid model is particularly needful for the development of new anticancer strategies and better measures for cancer treatment.
The SUPERBRAIN also designed the magnetic and plasmonic active nanocarriers which has drug and cancer cell targeting molecules on the surface. The innovative magnetic core shell noncarriers, target the 3D multicellular tumor spheroids under externally applied magnetic field and delivering the cancer drugs into 3D complex tumor type architecture. The SUPERBRAIN provides systematic approach for brain cancer therapeutics based on nanotechnology. Particles called nano-carriers also a key ingredient of most cancer therapies do the job well. But each nano-carrier or nanomedicine product is compatible with a limited range of drugs, and only a few can get succeed to target the tumor, meaning the vast majority of nanocarriers can’t be given as potentially to the target site. A SUPERBRAIN’s scientific developments has invented a novel nano-carrier, tested it in lab conditions on 3D multicellular cancer spheroids, and nanocarriers enables us to deliver drugs very precisely to solid tumors. Side effects that result from the drug ending up elsewhere in the body can be significantly reduced for paediatric cancer patients in the near future.
SUPERBRAIN’s, overall implementation designed plans and strategies to be applied in order to achieve a high level of visibility of the project outcomes and to transfer knowledge and results. SUPERBRAIN is a project that arises from the need of the European Union’s Mission: Cancer (2021-2030) focuses on the development of more accurate and targeted cancer therapies. Early diagnosis, and target more deprived populations in cancer prevention to open the new therapeutics window of cancer in small children using nanomedicine approach is the gaol of the SUPEBRAIN. This next generation technological marvel should be market ready to integrate them with clinics and meet all the legal and functional requirements that different health sectors demand.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

SUPERBRAIN’s scientific work packages reported the versatile magnetic and optical properties of the gold-magnetic (Au@Fe3O4) core shell NPs, this NPs have attracted increasing interest for magnetic, and light activated (remotely controlled) cancer theranostics. Gold shell can provide biocompatible and bio affinity through functionalization of amine/thiol terminal groups that can allow further bioconjugation of polymers, antibodies, drug molecules and DNA aptamers. In addition, gold layer can provide chemical stability to magnetic NPs by protecting the magnetic core from aggregation, oxidation, and corrosion functional surface. Therefore, the aim of this study was to develop a core shell magneto-plasmonic Au@Fe3O4 nanocarriers functionalized with polyethylene glycol, FDA-approved chemotherapeutic drug for childhood brain cancer including doxorubicin (DOX), and nucleolin targeted DNA aptamer AS1411. As DNA aptamer AS1411 are an integral player to targets nucleolin (a protein which is overexpressed in many cancer cells) and recently validated for brain cancer cell targeting37. In the next we developed 3D MCT spheroid model of low- and high-grade glioma, aggressive diffuse intrinsic pontine glioma and neuroblastoma cancer using liquid overlay technique, consisting of a direct co-culture of both neuronal and glial cells. Having validated the preclinical relevancy of the lab grown 3D MCT spheroid model, we aimed to investigate the effects of magnetic and light activated nanocarriers delivery into 3D MCT spheroids antitumor activity on tumor growth. An increased antitumor effect of nanocarriers is observed under magnetic and light field at a low concentration. These data prove the externally stimulated magneto-plasmonic nanocarriers is highly useful for next generation cancer therapies for childhood cancers.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In particular, the progress of SUPERBRAIN, provides methods of treating brain cancer cells in a subject comprising: (i) administering to the magneto-plasmonic nanocarriers to deliver chemotherapeutic agent and applying to the subject external magnetic field to release the chemotherapeutic cargo from nanocarriers into 3D MCT cancer spheroids.
SUPERBRAIN aims to design novel pathway of the 3D multicellular tumors in the laboratory settings that will reduce the burden on the animal experiments in near future. SUPERBRAIN has supported EU goals under Horizon Europe via high-impact scientific research that will have numerous scientific, societal, and techno-economic impacts. SUPERBRAIN provides innovative methods and technology in early therapy response to high grade brain cancers for paediatric and adult cancer patients, to develop novel therapeutic approaches and treatment response for addressing the one of our major societal health emergencies of aggressive brain cancer. According to “Strategic Market Research LLP” the Brain cancer Treatment Market worth the global brain monitoring market will witness a robust CAGR of 7.2%, valued at $5.78 billion in 2021, expected to appreciate and reach $10.09 billion by 2030, confirms Strategic Market Research . In sum, SUPERBRAIN’s scientific outcomes are based on RRI (Responsible Research and Innovation) for fostering alignment between economy/research/technological/societal outcomes, to meet people's needs under different axes (e.g. science education, gender equity, open access, ethics, and citizen participation and UN SDG goal no 3 and relevant ones). Fellow researcher has contributed in the generation of academic knowledge for example edited and authored books. Dr. Thorat edited five books and written one authored book to internationally recognized publishers such as Elsevier and Institute of Physics (IOP). These books are widely referred by many institutes for their academic curriculum. According to WorldCat library resources published books are available in the world’s top University libraries

Preparing magneto-plasmonic nanocarriers

Drug delivery in the tumor spheroid

Three dimensional tumor spheroid model