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Self-Guided Supramolecular Cargo-Loaded Nanomotors with Chemotactic Behavior towards Cells

Significance Statement

Tumor cells and wounded tissues produce an excessive amount of hydrogen peroxide. Drug delivery agents that could actively search and locate the diseased areas based on gradient of disease signal molecules between disease areas and blood stream/normal tissues would be an improvement to current targeting drug delivery systems. Although vesicular drug delivery systems such as polymersomes or liposomes are already used routinely in the clinic, the efficiency of targeted drug delivery is still limited mainly because these structures rely almost exclusively on passive accumulations a result of the leaky vasculature formed by rapid tissue growth found in tumors. Wilson approach is to use self-assembly as a tool to construct catalytic nanomotors that are able to carry cargo and direct their movement via chemotaxis. We are aiming to solve one of the most fundamental unresolved challenges in nanomotor research: “The Fantastic Voyage” – application of nanomotors for targeted drug delivery and diagnostics where nanomotors are able to actively seek and precisely locate tumour tissues by following a concentration gradient provided by the tumour signalling molecules.

Here we report a self-assembled nanomotor system able to self-propel and self-guide in a gradient of hydrogen peroxide produced by neutrophil cells. This is the first proof of concept experiment of nanosize motors able to carry a drug cargo and sense sick cells.  The nanomotor is formed through the assembly of smart amphiphilic block polymers into bowl shape structures incorporating an active catalyst in their inner compartment. Of nanometer scale, these motors are ideal for drug delivery in blood vessels/interstitial tissues and particularly attractive in biomedical applications. 

About The Author

Daniela A. Wilson (neé Apreutesei) received her B.Sc. degree (Hon) in chemistry from “A. I. Cuza” University of Iasi, Romania, in 2001 and an M.S. degree (Hon) in environmental chemistry from the same university in 2003. In 2006 she received her PhD with distinction “summa cum laudae” from “Gh. Asachi” Technical University of Iasi, Romania. During her PhD she obtained two fellowships in Japan and UK as exchange PhD student and Marie Curie fellow. She then worked as postdoctoral researcher at University of Pennsylvania, Philadelphia, USA and Radboud University Nijmegen, Netherlands in the groups of Prof. Virgil Percec and Prof. Roeland Nolte on several topics in synthetic organic chemistry, organometallic chemistry, and supramolecular and polymer chemistry. In 2012 she was awarded an ERC starting grant to investigate nanomotors with autonomous propulsion in biological systems. In 2015 she was awarded the first Athena Award from the Netherlands Organisation for Scientific Research for her excellent scientific research. She is currently assistant professor at the Institute for Molecules and Materials, Radboud University. Her research interests span a broad range of topics at the interface of supramolecular chemistry, macromolecular chemistry, and nanotechnology. 

Self-Guided -Supramolecular- Cargo-Loaded -Nanomotors- with- Chemotactic -Behavior -towards Cells. Global Medical Discovery feature

Journal Reference

Angew Chem Int Ed Engl. 2015;54(40):11662-5.

Peng F1, Tu Y1, van Hest JC2, Wilson DA3.

Show Affiliations
  1. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands).
  2. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands). [email protected]
  3. Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen (The Netherlands). [email protected]

Abstract

Delivery vehicles that are able to actively seek and precisely locate targeted tissues using concentration gradients of signaling molecules have hardly been explored. The directed movement toward specific cell types of cargo-loaded polymeric nanomotors along a hydrogen peroxide concentration gradient (chemotaxis) is reported. Through self-assembly, bowl-shaped poly(ethylene glycol)-b-polystyrene nanomotors, or stomatocytes, were formed with platinum nanoparticles entrapped in the cavity while a model drug was encapsulated in the inner compartment. Directional movement of the stomatocytes in the presence of a fuel gradient (chemotaxis) was first demonstrated in both static and dynamic systems using glass channels and a microfluidic flow. The highly efficient response of these motors was subsequently shown by their directional and autonomous movement towards hydrogen peroxide secreting neutrophil cells.

© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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