The mechanical properties of nanoparticles, especially
those designed
for biomedical purposes, have a large impact on their performance
and have been scarcely studied. Thermoresponsive polymer-based nanoparticles
are increasingly being used in biomedical applications; therefore,
it is crucial to determine their thermomechanical response in the
regime beyond their volume phase transition temperature (VPTT). The
morphological characterization and comparison of thermoresponsive
nanogels (NGs), silica core nanogels (SiO2@NGs), and nanocapsules
(NCs) in liquids, both below and above the VPTT, are explored in this
study. We employed atomic force microscopy in Peak Force QNM mode
as well as dynamic light scattering, nanoparticle tracking analysis,
and cryogenic electron microscopy (cryo-TEM). Surprisingly, nanocapsules
presented increased resistance to deformation, when compared to nanogels,
above the VPTT. This was attributed to differences in the cross-link
density radial distribution between nanogels and nanocapsules derived
from the synthetic approach employed. In addition, the Young’s
modulus was calculated from nanoindentations and by computer simulations,
showing a significant change in NCs upon crossing the VPTT from MPa
to GPa. Conversely, NGs displayed a Young’s modulus in the
kPa range, both below and above the VPTT. The findings of this study
show that structural design and thermoresponsivity strongly influence
the thermomechanical properties of nanoparticles. This in turn needs
to be taken into consideration in the design of future nanocarriers.