(598f) Multiscale Analysis of Topically Applied Nanoparticulate Adhesives: Biodistribution and Biotransformation

In recent years, metal and metal oxide
nanoparticles have received increasing interest in the biomedical world due to
their high reactivity and versatility. ¹Despite
very promising approaches and proof of concepts, the distribution and complex
interaction of nanoparticles with the surrounding tissue are
still poorly understood and remains a major obstacle to translation. The
rational and meaningful development of nanomedicines
is only possible with a good grasp of nanoparticle fate on multiple length
scales.

Here we demonstrate the correlative and multiscale
analysis of a nanoparticulate tissue adhesive based
on hybrid ceria/bioglass nanoparticles. We shine
light on the biodistribution and biotransformation of
this complex metal oxide system by a multitude of techniques. One week after
topical application² of the nanoparticles
onto the subcutaneous tissue of a rat, we run elemental analysis on the
harvested organs to determine that nearly all particles have stayed in the
skin. We then identify skin regions with high nanoparticle content using MicroCT. Histological sectioning of said regions gives us
direct access to the nanoparticles and the surrounding tissue. We discover that
a major part of the nanoparticles have stayed in the subcutis
via XRF mapping of the histological skin sections. We then further identify and
characterize the surroundings of the nanoparticles by histological staining and
electron microscopy. Hence, we are able to show colocalization
of nanoparticles and macrophages. We then harness advanced material
characterization techniques such as Raman spectroscopy and ToF-SIMS
to further classify the surroundings of the
nanoparticles. Finally, using high-resolution FIB-SEM, we are able to show that
the nanoparticles are tightly confined inside
macrophage membranes.

In summary, we were able to harness a plethora of
advanced characterization techniques to gain insight on the biodistribution
and biotransformation of topically applied complex
nanoparticles. This work provides a roadmap for the multiscale analysis of
nanomaterials in tissue and thus provides the groundwork for the safe, relevant
and rational design of new nanomedicines.

(1)    Ramos, A. P.; Cruz, M. A.
E.; Tovani, C. B.; Ciancaglini,
P. Biomedical Applications of Nanotechnology. Biophys
Rev 2017, 9 (2), 79–89.
https://doi.org/10.1007/s12551-016-0246-2.

(2)    Lese, I.; Graf, D. A.;
Tsai, C.; Taddeo, A.; Matter, M. T.; Constantinescu, M. A.; Herrmann, I. K.;
Olariu, R. Bioactive Nanoparticle-Based Formulations Increase Survival Area of
Perforator Flaps in a Rat Model. PLOS ONE 2018, 13 (11),
e0207802. https://doi.org/10.1371/journal.pone.0207802.