Electron microscope image showing iron oxide particles inside a liposome "bubble" (MIT)
Currently, neuroscience researchers rely heavily on invasive procedures to stimulate and record the neural activity of experimental animals. A team of MIT scientists has constructed a type of heat-sensitive, magnetic nanoparticle that can deliver chemical stimulants deep into brain tissues and release them on demand, providing a new means to remotely modulate the behaviors of test subjects.
Liposomal particles are tiny bubble-like structures often consisting of phospholipids bilayers. Due to their biocompatibility, ability to entrap a variety of small and large molecules, and versatility to adopt a wide range of physicochemical and biological properties, liposomes are a popular carrier in biomedical science, capable of delivering anything from plasmid DNA for gene editing, to cytotoxic chemo-agents in cancer therapy.
Magnetic nanoparticles (MNPs) can be produced by adding iron oxide to these lipid bubbles. They are not only a good contrast agent in Magnetic Resonance Imaging (MRI) scans, but also a perfect vehicle to induce magnetic hyperthermia--a technique extensively used in oncology treatment. In a typical procedure, a colloid preparation made of nanoscale iron oxide compounds is injected directly to the vein that feed a tumor. The colloidal particles get heated up upon exposure to an alternating high-frequency magnetic field, which enables them to "bake" and eventually kill off cancerous tissues within the tumor.
For behavior and neuroscience study, scientists often use recording electrodes to trigger deep brain stimulation (DBS). DBS, which involves placing stimulating electrodes deep inside a subject's brain, is effective in treating neurodegenerative disorders such as Parkinson’s disease and essential tremor.
The MIT team aimed to develop a much gentler alternative to replace this invasive procedure. They utilized a so-called magnetogenetic approach--essentially deploying blood-brain barrier (BBB)-crossing MNPs to the targeted brain region and using the thermal energy generated by magnetic hyperthermia to release chemical stimulants encapsulated inside these lipid bubbles.
In the study, they observed the heat generated in the vincinity of their MNPs in the presence of alternating magnetic fields. About 20 seconds later, when the liposomal particles reached a temperature of 42 degrees celsius (107.6 °F), the entrapped drug molecules were seen escaping from the thermally sensitive MNP.
The authors hope that their innovative magnetogenetic approach can one day revolutionize how neuroscience researchers modulate and study intrinsic neural circuits.