School of Natural and Environmental Sciences

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Light-driven unidirectional molecular machines as targeted photodynamic therapy agents

Chemistry Seminar Series - Dr Robert Pal, Durham University

Date/Time: Tuesday 9 October, 14:00 - 15:00

Venue: Bedson Building Room 2.76

Abstract

An important need for personalised therapeutics is the effective targeted in vivo destruction of selected cells and cell types, that are currently being highlighted by emergence of powerful optogenetic strategies.

Using a new generation of light activated uni-directional molecular nanomachines (MNM) we have demonstrated their application to expedite cell death using single photon excitation in the UV domain (Nature, 548, 567, 2017).

We embarked to promote our “proof of principle” technology into in vivo biomedical applications using two photon (2PE) activation, as UV light activation in vivo has significant limitations associated with shallow tissue penetration and non-uniform excitation/activation, limiting the 3D precision required for therapeutics.

This direction in activation not only allow deeper tissue penetration to realise in vivo photodynamic therapy (PDT) development, but also remove UV radiation as a confounder of biomedical efficacy.

Since with 2PE MNM activation will only occur in a small truly diffraction limited 3D voxel it allows the next phase of targeted photodynamic therapy protocols and methods to be designed, as with careful chemical engineering of the MNMs cell type and target receptor specific binding can be facilitated with experimental therapeutic precision as small as a single cell.

We demonstrated that by scanning a safe dose of NIR light in a 3D raster pattern for a predetermined period of time and repetition, only the surface bound MNM bearing cancerous cells are lysed, whereas all ‘healthy’ neighbouring cells remain intact and unaffected.

Once fully developed and validated 2PE activation of cell type and condition specific MNMs could be potentially adopted as a new form of extremely high optical precision, facile and non-invasive Type IV PDT for cancer treatment.

Robert Pal,ξ,* Liu Dongdong,Richard S. Gunasekera, Víctor García-López, Lizanne G. Nilewskiand  James M. Tour

ξDepartment of Chemistry, Durham University, South Road, DH1 3LE Durham, UK

Department of Chemistry, Rice University, Houston, Texas 77005, USA

Biography

Robert Pal grew up in Hungary and graduated with the Highest Achievement award in Chemistry from KLTE University of Debrecen.

In 2004 he has moved to Durham to start a Ph.D with Prof. David Parker on Responsive Luminescent Lanthanide systems.

Completing his Ph.D in late 2007 he began to work as a Postdoctoral researcher within the Parker group, also working closely with Prof. Andrew Beeby, moving away from organic chemistry towards bio-physical chemistry, spectroscopy and microscopy.

In 2014 he has been awarded with a prestigious University Research Fellowship from the Royal Society to study the Development and Chemical Application of Phase Modulation Nanoscopy.

Robert is also the Technical Director of two successful University spin out company, SynDex Inst. and FScan Ltd. the later which has developed lanthanide technology to measure the level of citrate in seminal fluid samples for PCa detection.

His research interests are focused around the development of novel optical and super-resolution microscopy instrumentation and associated time-resolved techniques.

His research group also maintains an interest in lanthanide based sensors and imaging agents, including organelle specific probes and alternative responsive stains and Circularly Polarised Luminescence, Fast Multi-point Raman spectro/microscopy, SERS probes, Lanthanide doped up-converting nanoparticles and Unimolecular Nanomachines for Selected Therapeutics (Nature 2017).

Dr Robert Pal
Dr Robert Pal