Optically Controlled Drug Delivery Through Microscale Brain–Machine Interfaces Using Integrated Upconverting Nanoparticles

Author:

Víg Levente1ORCID,Zátonyi Anita1,Csernyus Bence1,Horváth Ágoston C.1ORCID,Bojtár Márton2ORCID,Kele Péter2ORCID,Madarász Miklós3ORCID,Rózsa Balázs345,Fürjes Péter6ORCID,Hermann Petra6,Hakkel Orsolya6,Péter László7ORCID,Fekete Zoltán18

Affiliation:

1. Research Group for Implantable Microsystems, Faculty of Information Technology & Bionics, Pázmány Péter Catholic University, H-1083 Budapest, Hungary

2. Chemical Biology Research Group, Institute of Organic Chemistry, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, Hungary

3. BrainVisionCenter, H-1094 Budapest, Hungary

4. HUN-REN Institute of Experimental Medicine, H-1083 Budapest, Hungary

5. Two-Photon Measurement Technology Research Group, The Faculty of Information Technology, Pázmány Péter Catholic University, H-1083 Budapest, Hungary

6. Microsystems Laboratory, Institute of Technical Physics and Materials Science, HUN-REN Centre for Energy Research, H-1121 Budapest, Hungary

7. Complex Fluid Research Department, Institute of Solid-State Physics and Optics, HUN-REN Wigner Research Centre for Physics, H-1121 Budapest, Hungary

8. Sleep Oscillation Research Group, Institute of Cognitive Neuroscience & Psychology, HUN-REN Research Center for Natural Sciences, H-1117 Budapest, Hungary

Abstract

The aim of this work is to incorporate lanthanide-cored upconversion nanoparticles (UCNP) into the surface of microengineered biomedical implants to create a spatially controlled and optically releasable model drug delivery device in an integrated fashion. Our approach enables silicone-based microelectrocorticography (ECoG) implants holding platinum/iridium recording sites to serve as a stable host of UCNPs. Nanoparticles excitable in the near-infrared (lower energy) regime and emitting visible (higher energy) light are utilized in a study. With the upconverted higher energy photons, we demonstrate the induction of photochemical (cleaving) reactions that enable the local release of specific dyes as a model system near the implant. The modified ECoG electrodes can be implanted in brain tissue to act as an uncaging system that releases small amounts of substance while simultaneously measuring the evoked neural response upon light activation. In this paper, several technological challenges like the surface modification of UCNPs, the immobilization of particles on the implantable platform, and measuring the stability of integrated UCNPs in in vitro and in vivo conditions are addressed in detail. Besides the chemical, mechanical, and optical characterization of the ready-to-use devices, the effect of nanoparticles on the original electrophysiological function is also evaluated. The results confirm that silicone-based brain–machine interfaces can be efficiently complemented with UCNPs to facilitate local model drug release.

Funder

National Development, Research and Innovation Office

Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund

Hungarian Brain Research Program

Hungarian Academy of Sciences

Horizon 2020

Publisher

MDPI AG

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