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Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction

Paper ID Volume ID Publish Year Pages File Format Full-Text
61 5 2016 10 PDF Available
Title
Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction
Abstract

Fluorescent imaging agents that can specifically highlight tumor cells could have a significant impact on image-guided tumor removal. Here, fluorescent nanoparticles (NPs) derived from hyaluronic acid (HA) are investigated. HA is a ligand for the receptor CD44, which is a common biomarker present on many primary tumor cells, cancer-initiating cells, and tumor-associated fibroblasts. In addition, a family of enzymes that degrade HA, called hyaluronidases (HYALs), are also overexpressed with increased activity in many tumors. We report the design and development of a panel of targeted imaging agents using the near-infrared (NIR) dye, Cy7.5, that was directly conjugated to hydrophobically-modified HA. Two different molecular weights of HA, 10 kDa and 100 kDa, and three different degrees of hydrophobic moiety conjugation (0, 10, and 30 mol%) were utilized to develop a panel of NPs with variable size that ranged from 50 to 400 nm hydrodynamic diameter (HD) depending HA molecular weight, extent of fluorescence quenching (25–50%), kinetics of cellular uptake, and targeting to CD44+ cells. The kinetics and energy-dependence of cellular uptake in breast and prostate cancer cell lines, MDA-MB 231 and PC-3 cells, respectively, showed increased uptake with longer incubation times (at 4 and 8 h compared to 1 h), as well as uptake at 37 °C but not 4 °C, which indicated energy-dependent endocytosis. NP uptake studies in the presence of excess free HA showed that pre-treatment of cells with excess high molecular weight (MW) free HA decreased NP uptake by up to 50%, while no such trend was observed with low MW HA. These data lay the foundation for selection of optimized HA-derived NPs for image-guided surgery.Statement of SignificanceHere, hyaluronic acid (HA), a well-studied biomacromolecule, is modified with a near infrared fluorophore and a hydrophobic moiety. The significance of this work, especially for imaging applications, is that the impact of HA molecular weight and the hydrophobic moiety conjugation degree on fluorescence and cell interaction can be predicted. With respect to existing literature, the eventual use of these HA-based NPs is image-guided surgery; thus, we focus on the dye, Cy7.5, for conjugation, which is more NIR than most existing HA literature. Furthermore, HA is a ligand for CD44, which is associated with cancer and tumor microenvironment cells. Systematic studies in this work highlight that HA can be tuned to maximize or minimize CD44 binding

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Keywords
Hyaluronic acid; Image-guided surgery; Intraoperative imaging; Near-infrared fluorescence; Cy7.5
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Near infrared fluorescent nanoparticles based on hyaluronic acid: Self-assembly, optical properties, and cell interaction
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 36, May 2016, Pages 112–121
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us