A Synergistic Strategy for Treating Metastatic Tumors and Neurodegenerative Disorders via Multifunctional Polypeptide-based Conjugates

The design of new polypeptide-based drug delivery carriers represents an opportunity for
diseases with unmet clinical needs, such as neurodegenerative disorders, by improving
pharmacokinetic and pharmacodynamic properties and providing better quality of life for the
patient. Taurine (2-aminoethanesulfonic acid) - the most abundant free amino acid in the human
body - plays a leading role in the nervous system and regulates mechanisms such as
neuroinflammation and antitumorigenic effects.
We designed polypeptide-based carriers using a three-arm star-shaped polyglutamate (st-PGA) and
functionalized it with a taurine moiety. We obtained and characterized a family of taurine
derivatives, performing subsequent crosslinking reactions through biodegradable and nonbiodegradable
strategies to generate final nanosystems with various sizes, conformation, and final
structures. After their physicochemical characterization, ex vivo studies verified their effectiveness.
The nanoparticles comprise two star-shaped polyglutamate-drug conjugates modified by different
crosslinking precursors and crosslinked using flow chemistry at different ratios. Preliminary results
from asymmetric flow field flow fractionation (AF4) coupled with multi-angle light scattering
(MALS) and UV detectors revealed that nanoparticle size decreases using different reactors on
microfluidics. Here, we propose using small-angle X-ray scattering (SAXS) to study these materials
to determine their size and conformation in solution and unravel their aggregation process. Of
particular interest, we aim to combine results from dynamic light scattering (DLS) and AF4
experiments with SAXS profiles to study the viscoelastic properties of polymer with relatively small
amounts of sample.