| Autor: |
Fei Wang, Ling Sum Liu, Pan Li, Cia Hin Lau, Hoi Man Leung, Y Rebecca Chin, Chung Tin, Pik Kwan Lo |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Materials Today Bio, Vol 15, Iss , Pp 100299- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2590-0064 |
| DOI: |
10.1016/j.mtbio.2022.100299 |
| Popis: |
Compared with siRNAs or other antisense oligonucleotides (ASOs), the chemical simplicity, DNA/RNA binding capability, folding ability of tertiary structure, and excellent physiological stability of threose nucleic acid (TNA) motivate scientists to explore it as a novel molecular tool in biomedical applications. Although ASOs reach the target cells/tumors, insufficient tissue penetration and distribution of ASOs result in poor therapeutic efficacy. Therefore, the study of the time course of drug absorption, biodistribution, metabolism, and excretion is of significantly importance. In this work, the pharmacokinetics and biosafety of TNAs in living organisms are investigated. We found that synthetic TNAs exhibited excellent biological stability, low cytotoxicity, and substantial uptake in living cells without transfection. Using U87 three-dimensional (3D) multicellular spheroids to mimic the in vivo tumor microenvironment, TNAs showed their ability to penetrate efficiently throughout the whole multicellular spheroid as a function of incubation time and concentration when the size of the spheroid is relatively small. Additionally, TNAs could be safely administrated into Balb/c mice and most of them distributed in the kidneys where they supposed to excrete from the body through the renal filtration system. We found that accumulation of TNAs in kidneys induced no pathological changes, and no acute structural and functional damage in renal systems. The favourable biocompatibility of TNA makes it attractive as a safe and effective nucleic acid-based therapeutic agent for practical biological applications. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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