Cellular Export Fate of Liposomal Spherical Nucleic Acids

被引:6
作者
Paranandi, Krishna S. [1 ,2 ]
Lee, Andrew [1 ,3 ]
Stanic, Nikola [4 ]
Mirkin, Chad A. [1 ,5 ]
机构
[1] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA
[2] Northwestern Univ, Interdisciplinary Biol Sci Program, Evanston, IL 60208 USA
[3] Northwestern Univ, Dept Chem & Biol Engn, Evanston, IL 60208 USA
[4] Northwestern Univ, Int Inst Nanotechnol, Evanston, IL 60208 USA
[5] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA
基金
美国国家卫生研究院;
关键词
spherical nucleic acids; cellular export; liposomes; macrophages; phospholipases; INTRACELLULAR FATE; RATIONAL VACCINOLOGY; BINDING PROTEIN; ENDOCYTOSIS; NANOPARTICLES; EXOCYTOSIS;
D O I
10.1021/acsnano.3c04608
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Liposomal spherical nucleic acids (LSNAs) are useful structures for oligonucleotide-based cell modulation because of their biocompatibility and ability to readily enter cells without transfection agents. Understanding LSNA trafficking is key to developing applications, but while much is understood about LSNA cell uptake, little is known about their export fate. Here, we study LSNA export through pulse-chase studies with fluorophore-labeled LSNAs. Our findings show that the components of LSNAs are differentially exported by cells, with the phospholipids showing 90-100% export and the oligonucleotides showing 30-45% export over 24 h in RAW264.7 macrophages. Despite the increase in the level of uptake of LSNAs, these percentages are not significantly influenced by whether the materials are taken up as LSNAs or as the individual components. The exported oligonucleotide material consists of a full-length oligonucleotide with the phospholipid anchor modified by loss of a fatty acid. The exported liposome-derived phospholipids also had a fatty acid removed. Moreover, the exported oligonucleotide-lysophospholipid conjugates retain immunostimulatory potential. These findings indicate that after cellular entry LSNAs are degraded into lysophospholipids, something to which they are susceptible due to the presence of hydrolyzable ester bonds. The export percentage of the resultant materials over 24 h is independent of the amount imported, such that greater initial import leads to a similar fold increase in exported material. This work therefore reveals an intracellular feature of LSNAs and shows that the enhanced uptake achieved with LSNAs can be exploited to maximize the amount of material subsequently exported, suggesting avenues for leveraging pharmacologic effects from exported LSNA components.
引用
收藏
页码:19000 / 19010
页数:11
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