Aggregate Formation of BODIPY-Tethered Oligonucleotides That Led to Efficient Intracellular Penetration and Gene Regulation

Autor: Yui Umehara, Yu Kimura, Kazuhito Tanabe, Teruyuki Kondo, Ryohsuke Kurihara, Kotaro Takeyama, Wataru Asahi
Rok vydání: 2019
Předmět:
Zdroj: ACS Applied Bio Materials. 2:4456-4463
ISSN: 2576-6422
DOI: 10.1021/acsabm.9b00631
Popis: Exogenous nucleic acids showed low efficiency regarding cellular uptake and low stability in biological conditions; therefore, a number of techniques have been developed to improve their basic properties. One of the best solutions is the application of nanosized particles consisting of oligonucleotides that penetrate the cell membrane without any additives and exhibit high stability in cells. In this report, we employed a simple approach to address the basic properties of nanoparticles of oligonucleotides in biological systems. We prepared BODIPY-labeled oligonucleotides that carried an exclusive modification at the strand end. BODIPY shows high hydrophobicity and fluorescent emission; therefore, the oligonucleotides formed nanosized aggregates in aqueous solution and their behaviors in cells or tissues were easily tracked. Detailed experiments revealed that aggregate formation was indispensable for the high cellular uptake of the oligonucleotides via scavenger-receptor-mediated endocytosis. In addition, the aggregates provided an efficient gene regulation in living cells and tumor tissues transplanted into mice.
Databáze: OpenAIRE