A dual mode nanophotonics concept for in situ activation of brain immune cells using a photoswitchable yolk-shell upconversion nanoformulation

Here, we introduce a nanophotonics concept for optically triggered activation of microglia. Specifically, we synthesized a yolk-shell structured mesoporous silica coated core-shell upconverting nanoparticles (UCNP@ysSiO₂). The nanoparticles are loaded with microglia activators-bacterial lipopolysaccharide (LPS) together with indocyanine green (ICG), and then capped with β-cyclodextrin (CD) via selective affinity of this compound to photoswitchable azobenzene (Azo). Upon exposure to NIR light, and subsequent trans- to cis photoisomerization of the Azo group induced by the upconversion light, dissociation of β-CD produces the release of LPS. The released LPS activates microglia through a toll-like receptor 4 mediated pathway, while ICG excited by its absorption of the 800 nm upconversion light, produces local heating, thus synergistically activating microglia through heat shock proteins. We propose that the controlled activation of microglia with deep tissue penetrating NIR triggered drug release, may provide a new strategy for in situ treatment of many brain diseases.