title: Remote modulation of neural activities via near-infrared triggered release of biomolecules.
abstract: The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research.
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore 117575, Singapore.
authors.forename: Rongcong
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Amol D
authors.initials: AD
authors.lastname: Jadhav
authors.affiliation: Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Zicong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Chan
authors.affiliation: Department of Physics and Materials Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
authors.forename: Jufang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, Singapore 117575, Singapore. Electronic address: biecch@nus.edu.sg.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong SAR, China; Shenzhen Research Institute, City University of Hong Kong, Shen Zhen, China. Electronic address: pengshi@cityu.edu.hk.
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation; D020100:Hydrogels / Q000737:chemistry*; D007259:Infrared Rays; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D018377:Neurotransmitter Agents; D011108:Polymers; D011758:Pyrroles; C067635:polypyrrole
keywords: Drug release; Localized delivery; Near infrared stimulation; Photosensitive hydrogel; Remote control of neural activity