Near-infrared light driven tissue-penetrating cardiac optogenetics via upconversion nanoparticles in vivo

This study determines whether near-infrared (NIR) light can drive tissue-penetrating cardiac optical control with upconversion luminescent materials. Adeno-associated virus (AAV) encoding channelrhodopsin-2 (ChR2) was injected intravenously to rats to achieve ChR2 expression in the heart. The upconversion nanoparticles (UCNP) NaYF4:Yb/Tm or upconversion microparticles (UCMP) NaYF4 to upconvert blue light were selected to fabricate freestanding polydimethylsiloxane films. These were attached on the ventricle and covered with muscle tissue. Additionally, a 980-nm NIR laser was programmed and illuminated on the film or the tissue. The NIR laser successfully captured ectopic paced rhythm in the heart, which displays similar manipulation characteristics to those triggered by blue light. Our results highlight the feasibility of tissue-penetration cardiac optogenetics by NIR and demonstrate the potential to use external optical manipulation for non-invasive or weakly invasive applications in cardiovascular diseases.