  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.
