posted on 2021-06-11, 21:13authored byYue Song, Mahmoud Elsabahy, Christina A. Collins, Sarosh Khan, Richen Li, Teri N. Hreha, Yidan Shen, Yen-Nan Lin, Rachel A. Letteri, Lu Su, Mei Dong, Fuwu Zhang, David A. Hunstad, Karen L. Wooley
Platelet-like
and cylindrical nanostructures from sugar-based polymers
are designed to mimic the aspect ratio of bacteria and achieve uroepithelial
cell binding and internalization, thereby improving their potential
for local treatment of recurrent urinary tract infections. Polymer
nanostructures, derived from amphiphilic block polymers composed of
zwitterionic poly(d-glucose carbonate) and semicrystalline
poly(l-lactide) segments, were constructed with morphologies
that could be tuned to enhance uroepithelial cell binding. These nanoparticles
exhibited negligible cytotoxicity, immunotoxicity, and cytokine adsorption,
while also offering substantial silver cation loading capacity, extended
release, and in vitro antimicrobial activity (as
effective as free silver cations) against uropathogenic Escherichia
coli. In comparison to spherical analogues, cylindrical and
platelet-like nanostructures engaged in significantly higher association
with uroepithelial cells, as measured by flow cytometry; despite their
larger size, platelet-like nanostructures maintained the capacity
for cell internalization. This work establishes initial evidence of
degradable platelet-shaped nanostructures as versatile therapeutic
carriers for treatment of epithelial infections.