EventProf. Khuloud T Al-Jamal

Rationale Design of Nanocarriers for Brain and Cancer Targeting

Brain disorders are on the rise accounting for almost 12% of world mortalities every year. Despite extensive research in drug development, brain disorders are still largely untreated due to the inability to deliver current therapeutics to the brain across the BBB. Chemically functionalized carbon nanotubes (f-CNT) constitute a novel class of nanomaterials with attractive physical, chemical and electronic properties. The key advantage of f-CNTs is the extremely high surface area to size ratio allowing a high degree of chemical functionalization making them invaluable tools for designing drug delivery systems to the brain. One of the most interesting characteristics of f-CNTs is their ability to translocate across plasma membranes and enter the cells either passively by direct translocation across membranes or actively via endocytosis. We hereby designed a range of amino functionalised CNTs for BBB targeting. Their passive and double targeting properties to the BBB and glioma have been investigated in mouse model using a wide range of qualitative and quantitative techniques. Indium 111 labeled MWNTs displayed brain uptake of ~2-5% ID/g, after intravenous administration in mice, which is significantly higher than any other reported values for other  nanomaterials [1].

KT-Al-Jamal-poster-figure1

Scheme 1 depicts brain targeting using carbon nanotubes.

Cancer is another challenging disease for which there is a need for delivery. The conventional therapeutic agents for cancer therapy do not  demonstrate specificity for target tumour compared to healthy cells, but rely on the general systemic biodistribution to achieve their therapeutic effect, therefore cancer therapy is usually terminated as a result of severe side effects caused by the therapeutic agents. Targeting the therapeutic drugs with magnetic force has shown to be a promising method to concentrate the therapeutic agents at the target site and to lower the administered dosage therefore reducing systemic side effects. A polymeric nanocapsule formulation capable of triple-modal fluorescence/MR/SPECT imaging was developed for magnetic targeting of superficial tumours. Parameters influencing magnetic targeting in vivo in mice and their optimisation in preparation for first-in-man studies were studied. Time-course imaging studies showed 2-3 fold enhanced tumour uptake upon the application of magnetic field at tumour site, compared to only passive targeting. Effective tumour suppression when combining magnetic targeting with low dose of the anticancer drug docetaxel was observed and this offers promise for magnetic targeting application in the clinic, to minimise systemic side effects in cancer therapy [2].

[1] Wang J, Rubio N, Kafa H, Al-Jamal KT*. Kinetics of functionalised carbon nanotube distribution in mouse brain after systemic injection: Spatial to ultra-structural analyses. J. Control. Rel. 2016. DOI:10.1016/j.jconrel.2015.12.039. [2] KT Al-Jamal*, J Bai, JT-W Wang,..QA Pankhurst. Magnetic drug targeting: Preclinical in vivo studies,
mathematical modeling, and extrapolation to humans. Nano Lett., 2016, DOI: 10.1021/acs.nanolett.6b02261

KT-Al-Jamal-poster-figure2

Scheme 2 depicts cancer imaging/therapy with triple-modal imaging
nanpcapsules.

About The Speaker

KT-Al-Jamal

Professor Khuloud T. Al-Jamal is a Chair of Drug Delivery & Nanomedicine, King’s College London. She is also a registered pharmacist at the General Pharmaceutical Council. She started her academic career as a lecturer at King’s College London in 2011.

She has completed her pre-registration pharmacy training at The University College London Hospital and was awarded the Overseas Research Award Scheme (ORSA) Scholarship from The University of London (2000-2004) to complete her PhD in Drug Delivery from The School of Pharmacy, University of London (currently known as UCL-School of Pharmacy).

She was awarded the prestigious CW Maplethorpe Research and Teaching Postdoctoral Fellowship from The University of London (2005-2007) to explore the use of cationic dendrimers as anti-angiogenic agents for growth inhibition of solid and metastatic tumours.

She has developed an extensive experience in designing and developing novel nanoscale delivery systems including dendrimers, liposomes, quantum Dots (QDs), polymers, viral vectors, chemically functionalised carbon nanotubes and graphene oxide. Her current work involves pre-clinical translation of novel nanomaterials designed specifically for drug, protein, nucleic acids and radionuclide delivery for therapeutic or diagnostic applications.

She was awarded and is managing a number of research projects funded by The Royal Society, Worldwide Cancer Research, EPSRC, BBSRC, FP6, FP7 and ITN Marie Curie research programmes. In February 2012, she was awarded the BBSRC New Investigator award exploring the use of chemically functionalised carbon nano-needles as vectors for delivering therapeutics across the BBB. In 2012, she was awarded the prestigious Royal Pharmaceutical Society Science Award in recognition for her outstanding scientific achievements in the field of Nanomedicine. She is a three-time winner of the Wellcome Trust Image Award (2014-2016).  She is a management and steering committee member of the London Centre for Nanotechnology, a consortium that builds around nanotechnology research conducted at King’s College London, University College London and Imperial College London.