Open AccessSulfation Modulates the Targeting Properties of Hyaluronic Acid to P-Selectin and CD44
Author(s) -
Deep Bhattacharya,
Denis Svechkarev,
Aishwarya Bapat,
Prathamesh Patil,
Michael A. Hollingsworth,
Aaron M. Mohs
Publication year - 2020
Publication title -
acs biomaterials science and engineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.082
H-Index - 50
ISSN - 2373-9878
DOI - 10.1021/acsbiomaterials.0c00115
Subject(s) - cd44 , hyaluronic acid , in vivo , tumor microenvironment , chemistry , receptor , sulfation , in vitro , cancer research , cell , microbiology and biotechnology , biophysics , nanotechnology , materials science , biochemistry , biology , tumor cells , genetics
Many targeting strategies can be employed to direct nanoparticles to tumors for imaging and therapy. However, tumors display a dynamic, heterogeneous microenvironment that undergoes spatiotemporal changes, including the expression of targetable cell-surface biomarkers. Here, we develop a nanoparticle system to effectively target two receptors overexpressed in the microenvironment of aggressive tumors. Hyaluronic acid (HA) was regioselectivity modified using a multi-step synthetic approach to alter binding specificities for CD44 and P-selectin to tumor cell interaction. The dual-targeting strategy utilizes sulfate modifications on HA that targets P-selectin, in addition to native targeting of CD44, which exploits spatiotemporal alterations in the expression patterns of these two receptors in cancer sites. Using biophysical characterization and in vitro studies, we demonstrate that modified HA nanoparticles effectively targets both P-selectin + and CD44 + cells, which lays the groundwork for future in vivo biomedical applications.