Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Metal Nanoparticles* ; Nanoparticles*; Humans ; RNA, Small Interfering/genetics ; Gold ; Endothelial Cells ; Silver ; Polyethylene Glycols

Drug delivery systems such as dendrimers, liposomes, polymers or gold/silver nanoparticles could be used to advance modern medicine. One significant pharmacological problem is crossing biological barriers by commonly used drugs, e.g., in the treatment of neurodegenerative diseases, which have a problem of the blood-brain barrier (BBB) restricting drug delivery. Numerous studies have been conducted to find appropriate drug carriers that are safe, biocompatible and efficient. In this work, we evaluate pegylated gold nanoparticles AuNP14a and AuNP14b after their conjugation with therapeutic siRNA directed against APOE4. This genetic risk factor remains the strongest predictor for late-onset Alzheimer's disease. The study aimed to assess the biophysical properties of AuNPs/siAPOE complexes and to check their biological safety on healthy cells using human brain endothelial cells (HBEC-5i). Techniques such as fluorescence polarization, circular dichroism, dynamic light scattering, ζ-potential measurements and gel retardation assay showed that AuNPs form stable complexes with siRNA. Subsequently, cytotoxicity assays proved the biological safety of formed conjugates. Obtained results enabled us to find effective concentrations of AuNPs when complexes are formed and non-toxic for healthy cells. One of the studied nanoparticles, AuNP14b complexed with siRNA, displayed lower cytotoxicity (MTT assay, cells viability -74.8 ± 3.1%) than free nanoparticles (44.7 ± 3.6%). This may be promising for further investigations in nucleic acid delivery and could have practical use in treating neurodegenerative diseases.

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2018/30/Z/NZ1/00911 National Science Centre of Poland; 2018/ 31/F/NZ5/03454 National Science Centre of Poland; PID2020- 112924RBI00 MINECO

Keywords: biophysical interaction; complex formation; cytotoxicity; gold nanoparticles; siRNA

0 (RNA, Small Interfering)
7440-57-5 (Gold)
3M4G523W1G (Silver)
3WJQ0SDW1A (Polyethylene Glycols)

Date Created: 20230413 Date Completed: 20230414 Latest Revision: 20230415

20240628

PMC10094790

10.3390/ijms24076638

37047610