Hyaluronic Acid-Mediated Phenolic Compound Nanodelivery for Cancer Therapy

Phenolic compounds are bioactive phytochemicals showing a wide range of pharmacological\r\nactivities, including anti-inflammatory, antioxidant, immunomodulatory, and anticancer effects.\r\nMoreover, they are associated with fewer side effects compared to most currently used antitumor\r\ndrugs. Combinations of phenolic compounds with commonly used drugs have been largely studied\r\nas an approach aimed at enhancing the efficacy of anticancer drugs and reducing their deleterious\r\nsystemic effects. In addition, some of these compounds are reported to reduce tumor cell drug\r\nresistance by modulating different signaling pathways. However, often, their application is limited\r\ndue to their chemical instability, low water solubility, or scarce bioavailability. Nanoformulations,\r\nincluding polyphenols in combination or not with anticancer drugs, represent a suitable strategy\r\nto enhance their stability and bioavailability and, thus, improve their therapeutic activity. In recent\r\nyears, the development of hyaluronic acid-based systems for specific drug delivery to cancer cells has\r\nrepresented a pursued therapeutic strategy. This is related to the fact that this natural polysaccharide\r\nbinds to the CD44 receptor that is overexpressed in most solid cancers, thus allowing its efficient\r\ninternalization in tumor cells. Moreover, it is characterized by high biodegradability, biocompatibility,\r\nand low toxicity. Here, we will focus on and critically analyze the results obtained in recent studies\r\nregarding the use of hyaluronic acid for the targeted delivery of bioactive phenolic compounds to\r\ncancer cells of different origins, alone or in combination with drugs.