Binding and Internalization in Receptor‐Targeted Carriers: The Complex Role of CD44 in the Uptake of Hyaluronic Acid‐Based Nanoparticles (siRNA Delivery). Issue 24 (18th November 2019)

• Record Type: Journal Article
• Authors: Rios de la Rosa, Julio M.; Pingrajai, Ponpawee; Pelliccia, Maria; Spadea, Alice; Lallana, Enrique; Gennari, Arianna; Stratford, Ian J.; Rocchia, Walter; Tirella, Annalisa; Tirelli, Nicola
• Is Part Of: Advanced healthcare materials. Volume 8:Issue 24(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-11-18
• Subjects: cancer -- CD44 -- hyaluronic acid -- internalization -- nanocarriers -- RNA -- silencing -- targeted drug delivery; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201901182
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: CD44 is an endocytic hyaluronic acid (HA) receptor, and is overexpressed in many carcinomas. This has encouraged the use of HA to design CD44‐targeting carriers. This paper is about dissecting the mechanistic role of CD44. Here, HA‐decorated nanoparticles are used to deliver siRNA to both tumoral (AsPC‐1, PANC‐1, HT‐29, HCT‐116) and non‐tumoral (fibroblasts, differently polarized THP‐1 macrophages, HUVEC) human cell lines, evaluating the initial binding of the nanoparticles, their internalization rate, and the silencing efficiency (cyclophilin B (PPIB) gene). Tumoral cells internalize faster and experience higher silencing than non‐tumoral cells. This is promising as it suggests that, in a tumor, HA nanocarriers may have limited off‐target effects. More far‐reaching is the inter‐relation between the four parameters of the study: CD44 expression, HA binding on cell surfaces, internalization rate, and silencing efficiency. No correlation is found between binding (an early event) and any of the other parameters, whereas silencing correlates both with speed of the internalization process and CD44 expression. This study confirms on one hand that HA‐based carriers can perform a targeted action, but on the other it suggests that this may not be due to a selective binding event, but rather to a later recognition leading to selective internalization. Abstract : Hyaluronic acid (HA) is used for CD44‐targeted therapies. The evidence points to CD44 possibly being a selective internalizer rather than a primary binder for HA, which implies that a first (unselective?) receptor may be involved in HA capture before trafficking to CD44.