2024/06/04 by Thorsten Gölz, Gölz, Thorsten, Enrico Baù +15
Biochemistry, Genetics and Molecular Biology · #Applied Physics (physics.app-ph) #FOS: Physical sciences #Lipid Membrane Structure and Behavior #Optics (physics.optics) #RNA Interference and Gene Delivery #Spectroscopy Techniques in Biomedical and Chemical Research
paper · pdf · doi:10.48550/arxiv.2406.02513
openalex publication_date 2024/06/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Understanding the biophysical and biochemical properties of molecular nanocarriers under physiological conditions and with minimal interference is crucial for advancing nanomedicine, photopharmacology, drug delivery, nanotheranostics and synthetic biology. Yet, analytical methods struggle to combine precise chemical imaging and measurements without perturbative labeling. This challenge is exemplified for azobenzene-based photoswitchable lipids, which are intriguing reagents for controlling nanocarrier properties on fast timescales, enabling, e.g., precise light-induced drug release processes. Here, we leverage the chemical recognition and high spatio-temporal resolution of scattering-type scanning near-field optical microscopy (s-SNOM) to demonstrate non-destructive, label-free mid-infrared (MIR) imaging and spectroscopy of photoswitchable liposomes below the diffraction limit and the tracking of their dynamics down to 50 ms resolution. The vesicles are adsorbed on an ultrathin 10-nm SiN membrane, which separates the sample space from the tip space for stable and hour-long observations. By implementing a transient nanoscopy approach, we accurately resolve, for the first time, photoinduced changes in both the shape and the MIR spectral signature of individual vesicles and reveal abrupt change dynamics of the underlying photoisomerization process. Our findings highlight the methods potential for future studies on the complex dynamics of unlabeled nanoscale soft matter, as well as, in a broader context, for host-guest systems, energy materials or drugs.