Journal article
Small RNA stabilization via non-covalent binding with a metalloporphyrin nanocage to accomplish synergistic gene and photodynamic therapy
Department of Chemistry, Technical University of Denmark1
Center for Microbial Secondary Metabolites, Centers, Technical University of Denmark2
Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark3
Department of Health Technology, Technical University of Denmark4
Colloids & Biological Interfaces, Biotherapeutic Engineering and Drug Targeting, Department of Health Technology, Technical University of Denmark5
City of Hope National Med Center6
National Centre for Nano Fabrication and Characterization, Technical University of Denmark7
Nanocharacterization, National Centre for Nano Fabrication and Characterization, Technical University of Denmark8
Organic and Inorganic Chemistry, Department of Chemistry, Technical University of Denmark9
DTU Microbes Initiative, Centers, Technical University of Denmark10
...and 0 moreSmall RNAs (sRNAs) have emerged as attractive therapeutic agents due to their gene-editing and -regulatory properties. However, their application is severely limited by their relatively short circulation half-lives. Herein, we report a strategy binding sRNA with metalloporphyrin cages that leads to a significant protection of sRNA against RNase degradation and increased half-lives.
Nuclear magnetic resonance (NMR) titration of nucleosides and nucleotides demonstrates that π-stacking and electrostatic interactions contribute to the sRNA binding, which occurs on the external surface of the nanocage. Moreover, the cage binding promotes sRNA internalization, and the sRNAs maintain genetic activity after release in an acidic intracellular environment.
Taking advantage of the photodynamic properties of the cage, the nanosystem shows efficient in vitro cell killing through gene regulation and photodynamic effects, providing evidence for its therapeutic potential in breast cancer treatment. We envision the proposed strategy may provide new insight for the development of organometallic cage-based sRNA delivery vehicles.
Language: | English |
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Year: | 2022 |
ISSN: | 26663864 |
Types: | Journal article |
DOI: | 10.1016/j.xcrp.2022.101187 |
ORCIDs: | Jin, Weiguang , Xin, Li , Veiga, Gael Clergeaud , Hong Lin, Marie Karen Tracy , Andresen, Thomas Lars , Gotfredsen, Charlotte Held , Nielsen, Martin , Astakhova, Kira and Qvortrup, Katrine |