In vivo systemic toxicity of silica nanoparticles: Effects of sex, dose, and nanoparticle physicochemical properties
Journal of Controlled Release, cilt.397, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 397
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jconrel.2026.115187
- Dergi Adı: Journal of Controlled Release
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Anahtar Kelimeler: Accumulation, Animal sex, Dosing frequency, Nanomedicine, Nanotoxicology, Physicochemical properties, Silica nanoparticles
- İnönü Üniversitesi Adresli: Evet
Özet
Silica nanoparticles (SNPs) have been extensively studied for their applications in delivering bioactive agents. Studies have shown promising results of SNP-based delivery systems in terms of in-vitro biological assays, in-vivo bioavailability, and efficacy studies. However, the toxicity concerns of these inorganic nanoparticle systems have been considered a critical gap in clinically translating these particles as nanocarriers for intravenous delivery applications. For inorganic nanoparticle-based drug delivery systems, the role of nanoparticle physicochemical properties such as size, shape, porosity, and surface modification has a profound impact on biodistribution, pharmacokinetics, clearance, and associated toxicity. There is also limited information on how these physicochemical properties correlate with sex and dose-dependent toxicity. Answering these questions will help establish a knowledge-based platform for optimizing nanoparticle-based drug delivery systems with minimal toxic response. Herein, we established the maximum tolerated doses (MTD) of six SNP groups: nonporous 50 and 100 nm SNPs, mesoporous 100 nm SNPs, PEGylated mesoporous 100 and 500 nm SNPs, and rod-shaped (100: 200 nm) mesoporous SNPs in a BALB/c mouse model. From the MTD study, we selected four SNP-groups (nonporous 100 nm SNPs, mesoporous 100 nm SNPs, PEGylated mesoporous 100 nm SNPs, and rod-shaped (100: 200 nm) mesoporous SNPs), saline as a negative control group, and an empty 100 nm PEGylated liposomal system (Doxosome™, similar formulation to Doxil® in size and lipid composition without the loaded drug) as a clinical control group to do a comparative study of the accumulation of these SNPs in reticuloendothelial organs, as well as the associated blood, organ, and tissue-level toxicity, in a four-week single-dose and repeated half-dose study in male and female BALB/c mice. The study revealed that porous SNPs have a lower tolerated dose than nonporous SNPs; rod-shaped mesoporous SNPs have a lower tolerated dose than spherical mesoporous SNPs; and surface PEGylation can significantly increase the tolerated dose. At the maximum tolerated dose for each SNP-treated group, we did not observe toxicity at the blood, organ, or tissue levels. The study demonstrated promising results for the future clinical translation of SNP-based drug delivery systems.