ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

A study on co-modification of MSNs with some transition metals and polyethyleneimine (PEI) as a versatile strategy for efficient delivery of short oligonucleotides

Rafatosadat Badihi, Ali Mahmoudi, Mohammad Reza Sazegar, and Khodadad Nazari

Faculty of Chemistry, North Tehran Branch, Islamic Azad University, Hakimiyeh, Tehran, Iran

E-mail: mahmoudiali.ac@gmail.com

Received: 15 February 2022  Accepted: 20 July 2022

Abstract:

In this research, mesoporous silica nanoparticles (MSNs) were synthesized and hydrothermally modified with different transition metals, including Co²⁺, Fe²⁺, and Zn²⁺. The obtained samples (M-MSN) were further modified with polyethyleneimine (PEI) to give PEI-M-MSNs. These were studied for adsorption and desorption of siRNA molecules from phosphate-buffered saline (PBS). A direct relationship was observed between the adsorption capacity of each modified MSN sample and its zeta potential. As a result of high cationic nature of the PEI modifier and low ionic radius of Zn²⁺, PEI-Zn-MSN showed the highest siRNA adsorption capacity. Release of siRNA from the PEI-ZnMSN was just as good as its adsorption (37.6 vs. 42.5 µg/mg). Zeta potential of the samples seems to be a more important factor than their specific surface area. Pure MSN with the BET surface area of 1060 m² g⁻¹ showed the lowest siRNA adsorption capacity. PEI-Co-MSN, on the other hand, showed an unexpected low BET surface area of 208.9 m² g⁻¹. The very low adsorption capacity of the PEI-Co-MSN can be attributed to the destruction of the mesoporous framework, caused by the formation of Co₃O₄ nanoparticles, according to the XRD results. To obtain a sustained release profile, effect of the polyethyleneglycol (PEG) was studied. When a layer of PEG polymer was grafted on the surface, a sustained release profile was achieved and the PEGylated vehicle (PEG-PEI-Zn-MSN) showed tolerable cytotoxicity against normal human fibroblast cells according to the MTT test. The results of the present study may introduce the PEG-PEI-Zn-MSN as a versatile vehicle for efficient siRNA delivery.

Keywords: siRNA; Delivery; MSN; Modification; Zinc; PEI

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02387-7

Chemical Papers 76 (11) 7023–7035 (2022)