Hyaluronan as a therapeutic target in human diseases

Abstract

Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

Serum Hyaluronic Acid Levels Are Altered in Acute Leukemia Patients: Potential Prognostic Implications

“…1). In earlier studies, considerably elevated serum HA values have been observed in AML [26], multiple myeloma [29], malignant lymphoma [30], myelofibrosis, and CML [31], and also in various nonhematological diseases [13]. These studies confirmed that elevated serum HA levels may accompany malignant diseases.…”

“…It has also been detected in the bone marrow matrix, as an essential component [2]. Several studies have reported that HA levels are increased in a variety of human diseases [13] such as liver fibrosis and cirrhosis [14], diabetes [15,16], heart diseases [15], and lung fibrosis [13]. The role of HA in several malignancies such as breast cancer [17,18] and malignant pleural mesothelioma [19], has already been extensively investigated [3,6,20,21].…”

Paclitaxel-loaded hyaluronan solid nanoemulsions for enhanced treatment efficacy in ovarian cancer

“…The CD44-HA ligand-receptor pair is well known for its active tumor-targeting efficacy in cancer therapy. 14,[20][21][22][23] The targeting delivery systems such as nanoparticles, polymeric micelles, liposomes, emulsions, and nanogels with HA provide several advantages as drug carriers in both active and passive targeting of tumor receptors for drug delivery. 8,10,24,25 However, there are still several limitations, including low tumor-targeting efficacy, low bioavailability, undesirable tissue distribution, low drug loading dose, the need for relatively large injection volumes, low antitumor efficacy, unpredictable toxicity, and an initial drug release burst.…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…Antibodies (their size is about 12 nm) endowed with fluorescent dyes (e.g., Alexa Fluor 488 λEm=525 nm and Texas Red λEm=609 nm) [15][16][17] were used in the development of a wide range of effective targeted therapies [18][19][20][21][22] but they create clustering artifacts due to limited antibody penetration, which have an impact on insufficient labeling density. Thus, ligands that have been exploited for chemotherapeutic agent targeting systems can include monoclonal antibodies [23][24][25][26][27][28] but also low molecular weight receptor-binding conjugates such as dyelabeled peptides (arginine-glycine-aspartic acid-Cyt5,5) [29], peptide hormones [30,31], receptor antagonist and agonists [32], aptamers [33][34][35], transferrin [36][37], oligosaccharides [38], glycoconiugates [39], polyunsaturated fatty acids [40], oligopeptides [41,42], vitamin B12 [43], folic acid [44][45][46][47][48][49][50][51][52][53][54] and hyaluronic acid [55,56]. These ligands can be regarded as a tumor-specific receptor to construct a "guided molecular ...…”