Carbon Quantum Dots Assisted Virus Tracking: From Skin to Brain

Abstract Incurable infection by herpes simplex virus 1 (HSV‐1) can cause severe encephalitis and neurodegenerative diseases, e.g., Alzheimer's disease (AD) and amyotrophic lateral sclerosis. How HSV‐1 reaches the brain from the initial infection site remains inconclusive. Here, an innovative approach combining carbon quantum dots (CQDs) with dissolving microneedles (dMN) for real‐time tracking of HSV‐1 from skin to brain is presented. Upon application, CQDs‐HSV‐1 is released from the dMN through the swelling of interstitial fluid (ISF) in skin and subsequently monitored by living imaging. Remarkably, it is observed that HSV‐1 preferentially infects peripheral skin nerves, almost all viruses directly enter to brain via the spinal cord within 10–30 min, while few viruses enter the brain through the bloodstream via tail vein injection at the same time. Spinal cord injury (SCI) significantly delays the HSV‐1 transport from skin to brain but has no effect on the virus's travel from blood to brain. In a microfluid system, HSV‐1 shows preferential neurite infection, then transports to the cell body of differentiated SH‐SY5Y cells, highlighting the viral traffic process in neurons. The integration of CQDs‐virus labelling technology and dMN delivery model presents a promising tool for investigating the in vivo transport routes of neurotropic viruses with initial skin infections.