Hyaluronic acid targeting of CD44 for cancer therapy: from receptor biology to nanomedicine

Abstract

Cluster of differentiation-44 (CD44) is a ubiquitously present glycoprotein on the surface of mammalian cells that plays a significant role in a number of biological functions. Since the discovery that the receptor is over-expressed in a variety of solid tumors, such as pancreatic, breast and lung cancer, many studies have focused on methods for targeting CD44 in an attempt to improve drug delivery and discrimination between healthy and malignant tissue, while reducing residual toxicity and off-target accumulation. In this review, we describe CD44 receptor biology and its involvement in the different stages of tumor growth and metastasis, as well as methods currently used for targeting the receptor. Hyaluronic acid, the primary CD44 binding molecule, has proved a significant ally in developing nanocarriers that demonstrate preferential tumor accumulation and increased cell uptake. We outline a number of research approaches from the current literature that take advantage of hyaluronic acid’s targeting ability and describe the possible advantages for each approach. The value of CD44 targeting can be easily appreciated from the number of different approaches that have reached clinical trials.

• CD44 biology
• CD44/HA targeting
• drug delivery
• hyaluronic acid
• nanoparticles

Acknowledgements

The authors deeply appreciate all the efforts of former and current postdoctoral associates and graduate students who have been involved in this project.

Declaration of interest

Our research on development of combinatorial-designed HA self-assembling nanocarriers is partially supported by the National Cancer Institute of the National Institutes of Health through grants U01-CA151452 and R21-CA179652.

Notes

* For publication in the special issue of the Journal of Drug Targeting in honor of Professor Robert Langer – recipient of the 2015 JDT Lifetime Achievement Award – edited by Professor Samir Mitragotri, University of California Santa Barbara.