Hyaluronic Acid-Heptamethine Dye nanoparticle for Theranostic Applications

Abstract

Recently, near-infrared (NIR) dyes have emerged as a potential tool for tumor imaging and targeted therapy. These organic dyes are characterized by high extinction coefficients and relatively large Stokes’ shifts. Among these NIR dyes, heptamethine dye, particularly IR-780 iodide was identified and investigated for their optical property, in vivo tumor imaging and therapy. However, IR-780 and other derivatives of heptamethine dye lack the selectivity towards cancer cells and exhibit very low photostability. At the same time, nanomaterial-based molecular probes, namely nanoprobes made impressive improvement in tumor targeting through the enhanced permeability and retention (EPR) effect of the tumor microvasculature or by the specific binding with tumor-associated ligands, such as tumor cell receptors, tumor extracellular matrix and enzymes. Here in this work, we present the synthesis of pyridinium derivative of heptamethine dye (IR-Pyr) and preparation of nanoparticle (HA-IR-Pyr) by using the electrostatic interaction between hyaluronic acid and IR-Pyr. The polymer encapsulation is found to improve photostability, targetable capability and expected to increase the in vivo circulation time due to the enhancement in surface area during nanoformulation. Localization in mitochondria, ability to generate singlet oxygen and in vitro cytotoxicity was compared among the three candidates (IR-780, IR-Pyr and HA-IR-Pyr).