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Bioscience Initiative - Universiteit Leiden

Bioscience Initiative

Bioscience Initiative
Leiden University

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Chemical approaches to control the in vivo behavior of nanomedicines

Van Leeuwenhoek Lecture on BioScience.

Thursday February 20 2020 at 16.00hrs.
Gorlaeus B├Ętawetenschappen LUMY 04.28
Alexander Kros

Alexander Kros is a full professor in Supramolecular Chemistry & Biomaterials Chemistry (LIC) since 2015. In 1995 he obtained his MSc in Chemistry (Radboud University, Nijmegen), in 2000 he defended his thesis: 'Amperometric biosensors based on conducting nanotubes", also in Nijmegen. From 2000-2001 he was a postdoc at Caltech, USA. From 2002-2009 he was Assistant professor (LIC) and from 2009-2015 Associate professor (LIC). 

He uses supramolecular approaches in a biological environment. His main interest is in understanding the underlying fundamentals of membrane fusion in Nature using model systems and utilize he obtained knowledge to design new drug delivery tools.

Nanomedicines aim to deliver sensitive or toxic therapeutics in a cell or tissue in a highly selective manner. Through nanocarrier encapsulation and/or conjugation, the pharmacokinetics (e.g. biostability and availability) and/or tissue distribution of drugs within the body can be modified. By shifting the balance between off-and on-targeting, nanomedicines can minimize adverse (toxic) side effects, reduce drug dosages and ultimately deliver personalized (e.g. gene) therapies to patients.

A Google Scholar search, using the combined keywords "targeted", 'drug delivery" and "nanoparticles", reveals over 450.000 original research papers and reviews, spanning 30+ years. yet despite this huge effort and investment, there are currently just 4 antibody-drug conjugates and 14 nanoparticle-based therapies on the market. This low success rate clearly demonstrates nanomedicines have a delivery problem. Typically less than 1% of administered nanomedicines reach their intended target in the body and there has been no significant technolodgical advance to improve these meagre targeting efficiencies over the past 30 years.

In order to aid the design and study of novel nanomedicines my group uses zebrafish as an in vivo prescreening tool. Zebrafish are small-sized freshwater fish with widespread use in scientific research. As they have homologues for the vast majority of human genes, they are increasingly used as model organisms to study fundamental biological processes (e.g. embryogenesis, cell migration and disease pathogenesis). Their size and transparency enables high-resolution light microscopy imaging of these processes across entire organisms, down to the cellular level and in real time. (Fluorescent) transgenic lines are readily available or can be quickly generated using modern molecular biology tools (e.g. CRISPR-Cas9 and tol2-mediated transgenesis). The high speed, low cost and unprecedented (subcellular) resolution that can be obtained over entire living organisms has led to the larval zebrafish being rapidly adopted, within drug discovery pipelines, as an efficient, accurate and complementary model organism for in vivo prescreening of nanomedicines.

In this presentation I will present several examples of nanomedicines using novel chemical approaches and describe their biodistribution in zebrafish towards the development of functional nanomedicines.