On‐Demand Chemomagnetic Modulation of Striatal Neurons Facilitated by Hybrid Magnetic Nanoparticles

Abstract

Minimally invasive manipulation of cell signaling is critical in basic neuroscience research and in developing therapies for neurological disorders. Here, a wireless chemomagnetic neuromodulation platform for the on-demand control of primary striatal neurons that relies on nanoscale heating events is described. Iron oxide magnetic nanoparticles (MNPs) are functionally coated with thermoresponsive poly (oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) brushes loaded with dopamine. Dopamine loaded MNPs-POEGMA are co-cultured with primary striatal neurons. When alternating magnetic fields (AMF) are applied, MNPs undergo hysteresis power loss and dissipate heat. The local heat produced by MNPs initiates a thermodynamic phase transition on POEGMA brushes resulting in polymer collapse and dopamine release. AMF-triggered dopamine release enhances the response of dopamine ion channels expressed on the cell membranes enhancing the activity ≈50% of striatal neurons subjected to the treatment. Chemomagnetic actuation on dopamine receptors is confirmed by blocking D 1 and D 2 receptors. The reversible thermodynamic phase transition of POEGMA brushes allow the on-demand release of dopamine in multiple microdoses. AMF-triggered dopamine release from MNPs-POEGMA causes neither cell cytotoxicity nor promotes cell reactive oxygen species production. This research represents a fundamental step forward for the chemomagnetic control of neural activity using hybrid magnetic nanomaterials with tailored physical properties.

Applications of surface‐grafted polymer brushes with various architectures

“…(1) increase the bioavailability and solubility of drugs that helps to reduce the dose by changing the drug pharmacokinetics (into prolonged drug release profile), ( 2) target drug delivery to specific tissues, and/or (3) increase the uptake of drug carriers by specific cells (by enhanced permeability and retention effect). 100 PB have been applied in various systems for efficient delivery of anticancer 94,[101][102][103] and anti-inflammatory drugs, 104 neurotransmitters 105 and genes. [106][107][108] The main roles of PB in drug delivery systems are: the effective binding of bioactive compounds, the prevention of protein adsorption which prolongs the carrier's blood circulation and the influence on drug release profile (into sustained drug release or triggered by external stimuli).…”

“…Thermoresponsive POEGMA brushes were applied in systems developed by Guntnur et al for the on-demand chemomagnetic treatment of neurological disorders. 105 For this purpose, POEGMA brushes loaded with dopamine were grafted on iron oxide magnetic nanoparticles. The dopamine release was triggered by alternating magnetic fields-in these conditions iron oxide NPs produced local heat that caused reversible polymer collapse and controlled release of neurotransmitters in microdoses.…”

“…Thermoresponsive POEGMA brushes were applied in systems developed by Guntnur et al for the on‐demand chemomagnetic treatment of neurological disorders 105 . For this purpose, POEGMA brushes loaded with dopamine were grafted on iron oxide magnetic nanoparticles.…”

Cell-Membrane-Coated and Cell-Penetrating Peptide-Conjugated Trimagnetic Nanoparticles for Targeted Magnetic Hyperthermia of Prostate Cancer Cells

“…The magnetization measurements at the temperature T = 5 K revealed enhancement of the coercivity field, from H C ≈ 48.3 kA/m for the Fe 3 O 4 /MgO to H C ≈ 468.7 Oe for the Fe 3 O 4 /MgO/CoFe 2 O 4 nanoparticles, attributed to the magnetic coupling between both ferrimagnetic phases . To the best of our knowledge, no investigations about SAR assessment of this kind of nanoparticles can be found in the literature, thus representing TMNPs as a viable alternative to conventional hyperthermia where high doses of therapeutic agents are required. − …”

Conductive Conjugated Polymer Nanocapacitors for Localized Electrical Neurostimulation

“…8 Nanotechnology advances are enabling new neuromodulation modalities with deeper penetration, less invasiveness, improved biointerfaces, and higher spatiotemporal precision. 9 Wireless neuronal stimulation has recently been achieved using nanotechnology approaches like magnetomechanical actuation by magnetic discs, 10,11 magnetothermal transduction by magnetic nanoparticles, 12,13 chemomagnetic approaches, 14,15 photother-mal polymeric nanotransducers, 16 electric field generation using piezoelectric nanomaterials, 17 and photovoltaic effects from conjugated conductive polymers 18 or magnetoelectric materials. 19,20 In this vein, conjugated conductive polymers are receiving increasing attention due to their electrical and ionic conductivity, which make them ideal for neuronal stimulation.…”