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Title: Nano-enabled delivery of drugs and imaging agents to colorectal cancer cells in vitro and in vivo

Paul A Millner

University of Leeds, UK

Biography

Prof Paul Millner gained his PhD (Plant Sciences) in 1979 at the University of Leeds. After being a Research Fellow at Purdue University, Indiana and Imperial College, London he returned to the Dept of Biochemistry and Molecular Biology in Leeds in 1986 as a Lecturer in Biochemistry. After around 14 years as a molecular plant scientist his interests switched to bionanotechnology, and in particular interfacing biomolecules with no-biological surface to build functional devices; these include biosensors, light-driven water sterilization fabrics and targeted nanoparticle systems, both for biosensing and drug delivery. He has published around 150 articles of which around 100 are in peer reviewed journals.

 

Abstract

Nanoparticles in the size range below around 100 nm offer many advantages for bioscience and biomedicine. Essentially they can be considered as containers which can be used to package a payload, which might be a drug or imaging agent and sizes below 100 nm are needed to allow effective tissue penetration. Nanoparticles can be fabricated from a range of precursors and comprised of hydrophilic or hydrophobic reagents depending in the character of the payload, and can be solid or shell- particles. Although untargeted nanoparticles can accumulate to some extent in tumour tissue, particles that re targeted to an address tag, typically an over-expressed surface marker protein, show a much greater targeting efficiency, and permit much higher doses of particle payload to be delivered to the target site. In some cases they permit use of highly toxic drugs whose off-target toxicity would preclude their use if delivered normally.
     I will describe silica particles which can carry a substantial payload of water-soluble dyes for optical imaging, photosensitizers for photodynamic therapy and MRI contrast agents such as chelated gadolinium. These have been shown to target specifically to colorectal cancer (CoRC) cells in culture and to CoRC xenografts in immune compromised mice using a validated mAB against the CoRC biomarker carcinoembryonic antigen (CEA) or an Affimer, an artificial binding protein, against the same  target. I will also describe the fabrication and loading of cubic lipidic particles (“cubososomes”) with novel and cheap organo-copper reagents, and successful anti-CEA Affimer targeting of these nanocomposites to CoRc cells and xenografts. Again, using dye loaded cubosomes correct and specific targeting can be shown, and early indications are that the organ-copper reagents, which are potent cytotoxins operating via metabolic reactive oxygen generation, also target and are specifically able to kill cancer tissue in vivo, within our mouse xenograft model.
Audience take away:
• Nano-packaging of drugs into targeted nanoparticles
• Nanoparticles for packaging hydrophilic and hydrophobic drugs
• Targeted nano-packaged drugs can be sent directly the target tissue, thereby potentially reducing overall dose, and target effects
• Targeted nano-packaging of drugs could enable use of drugs that are too toxic to be delivered by simple systemic injection