Synthesis and characterization of amino acid-functionalized calcium phosphate nanoparticles for siRNA delivery

Bakan, Feray and Kara, Göknur and Çokol Çakmak, Melike and Çokol, Murat and Denkbaş, Emir Baki (2017) Synthesis and characterization of amino acid-functionalized calcium phosphate nanoparticles for siRNA delivery. Colloids and Surfaces B: Biointerfaces, 158 . pp. 175-181. ISSN 0927-7765 (Print) 1873-4367 (Online) Published Online First http://dx.doi.org/10.1016/j.colsurfb.2017.06.028

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Abstract

Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20–27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery. In this work, chemically and morphologically different calcium phosphate (CaP) nanoparticles, including spherical-like hydroxyapatite (HA-s), needle-like hydroxyapatite (HA-n) and calcium deficient hydroxyapatite (CDHA) nanoparticles were synthesized by the sol-gel technique and the effects of particle characteristics on the binding capacity of siRNA were investigated. In order to enhance the gene loading efficiency, the nanoparticles were functionalized with arginine and the morphological and their structural characteristics were analyzed. The addition of arginine did not significantly change the particle sizes; however, it provided a significantly increased binding of siRNA for all types of CaP nanoparticles, as revealed by spectrophotometric measurements analysis. Arginine functionalized HA-n nanoparticles showed the best binding behavior with siRNA among the other nanoparticles due to its high, positive zeta potential (+18.8 mV) and high surface area of Ca++ rich “c” plane. MTT cytotoxicity assays demonstrated that all the nanoparticles tested herein were biocompatible. Our results suggest that high siRNA entrapment in each of the three modified non-toxic CaP nanoparticles make them promising candidates as a non-viral vector for delivering therapeutic siRNA molecules to treat cancer.
Item Type: Article
Uncontrolled Keywords: Calcium phosphate; Hydroxyapatite nanoparticles; Gene delivery; Small interfering RNA (siRNA); Surface functionalization
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Materials Science & Eng.
Sabancı University Nanotechnology Research and Application Center
Faculty of Engineering and Natural Sciences
Depositing User: Feray Bakan
Date Deposited: 09 Sep 2017 16:11
Last Modified: 22 May 2019 13:54
URI: https://research.sabanciuniv.edu/id/eprint/32923

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