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

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.