Iodinated hyaluronic acid oligomer-based nanoassemblies for tumor-targeted drug delivery and cancer imaging

Biomaterials. 2016 Apr:85:218-31. doi: 10.1016/j.biomaterials.2016.01.060. Epub 2016 Jan 29.

Abstract

Nano-sized self-assemblies based on amphiphilic iodinated hyaluronic acid (HA) were developed for use in cancer diagnosis and therapy. 2,3,5-Triiodobenzoic acid (TIBA) was conjugated to an HA oligomer as a computed tomography (CT) imaging modality and a hydrophobic residue. Nanoassembly based on HA-TIBA was fabricated for tumor-targeted delivery of doxorubicin (DOX). Cellular uptake of DOX from nanoassembly, compared to a DOX solution group, was enhanced via an HA-CD44 receptor interaction, and subsequently, the in vitro antitumor efficacy of DOX-loaded nanoassembly was improved in SCC7 (CD44 receptor positive squamous cell carcinoma) cells. Cy5.5, a near-infrared fluorescence (NIRF) dye, was attached to the HA-TIBA conjugate and the in vivo tumor targetability of HA-TIBA nanoassembly, which is based on the interaction between HA and CD44 receptor, was demonstrated in a NIRF imaging study using an SCC7 tumor-xenografted mouse model. Tumor targeting and cancer diagnosis with HA-TIBA nanoassembly were verified in a CT imaging study using the SCC7 tumor-xenografted mouse model. In addition to efficient cancer diagnosis using NIRF and CT imaging modalities, improved antitumor efficacies were shown. HA and TIBA can be used to produce HA-TIBA nanoassembly that may be a promising theranostic nanosystem for cancers that express the CD44 receptor.

Keywords: Hyaluronic acid; In vivo imaging; Nanoassemblies; Triiodobenzoic acid; Tumor-targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Delivery Systems*
  • Hyaluronic Acid / chemistry*
  • Injections, Intravenous
  • Iodine / chemistry*
  • Mice
  • NIH 3T3 Cells
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy*
  • Spectroscopy, Near-Infrared
  • Tomography Scanners, X-Ray Computed
  • Triiodobenzoic Acids / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Triiodobenzoic Acids
  • Doxorubicin
  • Hyaluronic Acid
  • Iodine