title: Advances and advantages of nanomedicine in the pharmacological targeting of hyaluronan-CD44 interactions and signaling in cancer.
abstract: Extensive experimental evidence in cell and animal tumor models show that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to cancer therapy. Because of the intimate relationship between the hyaluronan-CD44 system and tumor cell survival and growth, it is an increasingly investigated area for applications to anticancer chemotherapeutics. Interference with the hyaluronan-CD44 interaction by targeting drugs to CD44, targeting drugs to the hyaluronan matrix, or interfering with hyaluronan matrix/tumor cell-associated CD44 interactions is a viable strategy for cancer treatment. Many of these methods can decrease tumor burden in animal models but have yet to show significant clinical utility. Recent advances in nanomedicine have offered new valuable tools for cancer detection, prevention, and treatment. The enhanced permeability and retention effect has served as key rationale for using nanoparticles to treat solid tumors. However, the targeted and uniform delivery of these particles to all regions of tumors in sufficient quantities requires optimization. An ideal nanocarrier should be equipped with selective ligands that are highly or exclusively expressed on target cells and thus endow the carriers with specific targeting capabilities. In this review, we describe how the hyaluronan-CD44 system may provide such an alternative in tumors expressing specific CD44 variants.
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
authors: Spyros S
authors: SS
authors: Skandalis
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece; Foundation for Research and Technology, Institute of Chemical Engineering Sciences (FORTH/ICE-HT), Patras, Greece.
authors: Chrisostomi
authors: C
authors: Gialeli
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.
authors: Achilleas D
authors: AD
authors: Theocharis
authors: Biochemistry, Biochemical Analysis and Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece; Foundation for Research and Technology, Institute of Chemical Engineering Sciences (FORTH/ICE-HT), Patras, Greece. Electronic address: n.k.karamanos@upatras.gr.
authors: Nikos K
authors: NK
authors: Karamanos
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D004337:Drug Carriers; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid
keywords: CD44; Cancer; Drug delivery; Hyaluronan; Nanomedicine; Nanoparticle; Pharmacological targeting