Pegylated Gold Nanoparticles Conjugated with siRNA: Complexes Formation and Cytotoxicity
2023
Okła, Elżbieta | Białecki, Piotr | Kędzierska, Marta | Pedziwiatr-Werbicka, Elzbieta | Takvor, Samuel | Gómez, Rafael | de la Malta, Francisco Javier | Bryszewska, Maria | Ionov, Maksim | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | Department of Organic and Inorganic Chemistry, Research Chemistry Institute “Andrés M. del Río” (IQAR), University of Alcalá, 28871 Alcalá de Henares, Spain; Networking Research Center for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain; Institute “Ramón y Cajal” for Health Research (IRYCIS), 28034 Madrid, Spain | Department of Organic and Inorganic Chemistry, Research Chemistry Institute “Andrés M. del Río” (IQAR), University of Alcalá, 28871 Alcalá de Henares, Spain; Networking Research Center for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain; Institute “Ramón y Cajal” for Health Research (IRYCIS), 28034 Madrid, Spain | Department of Organic and Inorganic Chemistry, Research Chemistry Institute “Andrés M. del Río” (IQAR), University of Alcalá, 28871 Alcalá de Henares, Spain; Networking Research Center for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain; Institute “Ramón y Cajal” for Health Research (IRYCIS), 28034 Madrid, Spain | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, Poland | [email protected]
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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