A novel radiolabelled multimodal nanocarrier system for tracking the delivery of therapeutic drugs and radionuclides in hard-to-treat cancers

Lead Research Organisation: University of Cambridge
Department Name: Chemical Engineering and Biotechnology

Abstract

Cancer is the second leading cause of death worldwide, with only 50% of diagnosed patients surviving a more than 10 years. Therapy using traditional chemotherapeutics is hindered due to lack of specificity, poor solubility and distribution of the drugs, unfavourable pharmacokinetics, and toxicity to healthy cells which results in severe side effects. The field of cancer theranostics has generated a vast amount of excitement due to the innovative ability to increase therapeutic selection on the basis of specific molecular disease hallmarks, improved foresight of possible adverse effects, and novel methods to empirically monitor response to the therapy. Targeted drug delivery systems are explored for the design of smart therapies capable of selective delivery of toxic drugs while also enabling detection of the delivery and post-drug release fate. In this project, we aim to reduce off-target toxicities and increase concentrations of therapeutic drugs in target organs. Combining effective cancer treatment with targeting abilities, paired with imaging and therapeutic efficiency will be a unique addition to the field of cancer nanomedicine. By achieving these objectives, this research will contribute a successful proof-of-concept therapy, which will greatly reduce off-target toxicities and increase overall therapy success.

This interdisciplinary project will harness knowledge across numerous departments at the University of Cambridge, and further expertise from Hitachi. The project will involve the synthesis of a multimodal nanocarrier system using porous polydopamine (PDA) nanocarriers decorated with chelating agents for binding radionuclides for imaging, capable of embedding the drug molecules within their cores and containing functional groups to bind cancer cell specific targeting agents for hard-to-treat cancers. Targeting agents will be explored in collaboration with Dr Daniel Munoz-Espin's group. The nanocarrier system will be assessed at each stage using both gold standard and novel state-of-the art technologies. Small animal PET studies will be carried out to gain important information on biodistribution.

The main outcome from this project will be the advancement of novel treatments for hard-to-treat cancers. In the long term, the research will contribute to the improvement of patient outcomes and quality of life by increasing the concentration and specificity of drugs that reach the tumour site. In the short term, clinicians, patients, regulatory authorities, and other stakeholders will benefit from the early involvement for a novel therapeutic solution. Researchers will benefit from the new scientific approaches and engineering methods that will be explored in this interdisciplinary project. The project optimises diagnosis and treatment and aids in the creation of novel therapies and approaches to drug delivery and targeted medicine. This project is aligned with the EPSRC's clinical technologies research area, with the help of the dynamic fields of bionanotechnology, drug delivery, radiology, and medical imaging.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/S023046/1 01/10/2019 31/03/2028
2276769 Studentship EP/S023046/1 01/10/2019 30/09/2023 Swetha Lingamgunta