@article{9eeed51e18774ab0a81404e797005e0d,
title = "Sulfation Modulates the Targeting Properties of Hyaluronic Acid to P-Selectin and CD44",
abstract = "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 multistep 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 target 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 target both P-selectin+ and CD44+ cells, which lays the groundwork for future in vivo biomedical applications.",
keywords = "CD44, Dual target, P-selectin, hyaluronic acid, near-infrared",
author = "Bhattacharya, {Deep S.} and Denis Svechkarev and Aishwarya Bapat and Prathamesh Patil and Hollingsworth, {Michael A.} and Mohs, {Aaron M.}",
note = "Funding Information: We thank Dr. Amarnath Natarajan for the fruitful scientific assistance in setting up the FP binding assay. We would also like to thank James Talaska and Janice Taylor at the UNMC Advanced Microscopy Core Facility which receives partial support from the National Institute for General Medical Science (NIGMS) INBRE - P20 GM103427 and COBRE - P30 GM106397 grants, as well as support from the National Cancer Institute (NCI) for The Fred and Pamela Buffett Cancer Center Support Grant - P30 CA036727 and the Nebraska Research Initiative. We would also like to thank Victoria Smith and Samantha Wall at the UNMC Flow Cytometry Research Facility, which is administrated through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffett Cancer Center{\textquoteright}s National Cancer Institute Cancer Support Grant. Major instrumentation has been provided by the Office of the Vice Chancellor for Research, The University of Nebraska Foundation, the Nebraska Banker{\textquoteright}s Fund, and the NIH-NCRR Shared Instrument Program. This work was funded by the National Institute of Biomedical Imaging and Bioengineering (R01 EB019449), the Fred and Pamela Buffett Cancer Center at UNMC (P30 CA036727), and the UNMC Program of Excellence fellowship awarded to Deep S. Bhattacharya. We would also like to thank Madeline Olson for her technical assistance in designing manuscript figures. Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",
year = "2020",
month = jun,
day = "8",
doi = "10.1021/acsbiomaterials.0c00115",
language = "English (US)",
volume = "6",
pages = "3585--3598",
journal = "ACS Biomaterials Science and Engineering",
issn = "2373-9878",
publisher = "American Chemical Society",
number = "6",
}