Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs

Nanomedicine (Lond). 2016 Jul;11(14):1865-87. doi: 10.2217/nnm-2016-5000. Epub 2016 Jul 7.


Extensive experimental evidence demonstrates the important role of hyaluronic acid (HA)-CD44 interaction in cell proliferation and migration, inflammation and tumor growth. Taking advantage of this interaction, the design of HA-modified nanocarriers has been investigated for targeting CD44-overexpressing cells with the purpose of delivering drugs to cancer or inflammatory cells. The effect of such modification on targeting efficacy is influenced by several factors. In this review, we focus on the impact of HA-modification on the characteristics of lipid-based nanoparticles. We try to understand how these modifications influence particle physicochemical properties, interaction with CD44 receptors, intracellular trafficking pathways, toxicity, complement/macrophage activation and pharmacokinetics. Our aim is to provide insight in tailoring particle modification by HA in order to design more efficient CD44-targeting lipid nanocarriers.

Keywords: CD44; grafting density; hyaluronic acid; lipid-based nanoparticles; pharmacokinetics; toxicity; trafficking pathways.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Drug Delivery Systems / methods*
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Hyaluronic Acid / analogs & derivatives*
  • Hyaluronic Acid / metabolism
  • Lipid Metabolism
  • Lipids / chemistry*
  • Liposomes / chemistry*
  • Liposomes / metabolism
  • Nanocapsules / chemistry
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism


  • Antineoplastic Agents
  • Hyaluronan Receptors
  • Lipids
  • Liposomes
  • Nanocapsules
  • Hyaluronic Acid