title: 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.
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA.
authors.forename: George
authors.initials: G
authors.lastname: Mattheolabakis
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA.
authors.forename: Lara
authors.initials: L
authors.lastname: Milane
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, Northeastern University , Boston , MA , USA.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000378:metabolism; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid
keywords: CD44 biology; CD44/HA targeting; drug delivery; hyaluronic acid; nanoparticles