Supramolecular Organization and siRNA Binding of Hyaluronic Acid-Coated Lipoplexes for Targeted Delivery to the CD44 Receptor

Abstract

Original Citation:Supramolecular organization and siRNA binding of hyaluronic acid-coated lipoplexes for targeted delivery to the CD44 receptor. Published version:DOI:10.1021/acs.langmuir.5b01979 Terms of use:Open Access (Article begins on next page) Anyone can freely access the full text of works made available as "Open Access". Works made available under a Creative Commons license can be used according to the terms and conditions of said license. Use of all other works requires consent of the right holder (author or publisher) if not exempted from copyright protection by the applicable law. Availability: This is the author's manuscript AbstractThe dynamics of the formation of siRNA-lipoplexes coated with hyaluronic acid (HA) and the parameters influencing their supramolecular organization were studied. The insertion of a HAdioleylphosphatidylethanolamine (DOPE) conjugate in the liposome structure as well as subsequent complexation with siRNA increased the liposome size. Lipoplexes were around 110 nm at high ± charge ratios with a zeta potential around +50 mV and around 230 nm at low ± ratios, with a zeta potential that decreased to negative values, reaching −45 mV. The addition of the conjugate did not compromise siRNA binding to liposomes, although these nucleic acids induced a displacement of part of the HA-DOPE conjugate upon lipoplex formation, as confirmed by capillary electrophoresis. Isothermal titration calorimetry, X-ray diffraction studies, and cryo-TEM microscopy demonstrated that in addition to electrostatic interactions with siRNA a rearrangement of the lipid bilayers takes place, resulting in condensed oligolamellar vesicles. This phenomenon is dependent on the number of siRNA molecules and the degree of modification with HA. Finally, the suitable positioning of HA on the lipoplex surface and its ability to bind specifically to the CD44 receptors in a concentrationdependent manner was demonstrated by surface plasmon resonance analysis.

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

“…We also observed that the HA and CD44 could specifically bind together. 27,28 The results suggest that the mechanism underlying the targeted therapy by siRNA might involve the reduced expression of CD44 in the ectopic endometria.…”

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy

“…The active targeting strategy was twofold. HA was used to target CD44 receptors overexpressed on the cellular surface of a variety of tumor carcinomas [85,86]. Additionally, GA-conjugated polymer drug delivery systems have recently been shown to actively target the liver to halt the progression of hepatic tumors [87–89].…”

Progress in the development of Lipoplex and Polyplex modified with Anionic Polymer for efficient Gene Delivery

“…HA can also be conjugated to lipids ( Figure 3B) or polymers (Figure 5B) using chemical linkers [36][37][38][39][40][41]. HA-DOPE conjugate can be obtained through the creation of an amide bond between the carboxylic groups of HA and the amino group of DOPE [37].…”

“…HA-DOPE conjugate can be obtained through the creation of an amide bond between the carboxylic groups of HA and the amino group of DOPE [37]. Inclusion of HA-DOPE conjugates into cationic liposomes composed of [2-(2,3-didodecyloxypropyl) hydroxyethyl] ammonium bromide (DC) and DOPE ( Figure 3B) could improve transfection into tumor cells expressing the CD44 receptor [36][37][38][39]. Furthermore, DOTAP/DOPE liposomes modi ied with HA-DOPE conjugate ( Figure 3B) also exhibited improved stability in cell culture medium and a reduced cytotoxicity [40].…”