Modulation of the lifespan of C. elegans by the controlled release of nitric oxide |
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Authors: | Dawei Jiang Lei Cheng Yudong Xue Chao Chen Chaochao Wang Guoliang Yang An Xu Youjun Yang Yun Gao Weian Zhang |
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Affiliation: | Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, Shanghai China.; Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 China.; School of Environmental Science and Optoelectronic Technology, University of Science and Technology of China, Hefei Anhui 230026 China, |
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Abstract: | The frontier of nitric oxide biology has gradually shifted from mechanism elucidation to biomanipulation, e.g. cell-proliferation promotion, cell-apoptosis induction, and lifespan modulation. This warrants biocompatible nitric oxide (NO) donating materials, whose NO release is not only controlled by a bioorthogonal trigger, but also self-calibrated allowing real-time monitoring and hence an onset/offset of the NO release. Additionally, the dose of NO release should be facilely adjusted in a large dynamic range; flux and the dose are critical to the biological outcome of NO treatment. Via self-assembly of a PEGylated small-molecule NO donor, we developed novel NO-donating nanoparticles (PEG-NORM), which meet all the aforementioned criteria. We showcased that a low flux of NO induced cell proliferation, while a high flux induced cell oxidative stress and, ultimately, death. Notably, PEG-NORM was capable of efficiently modulating the lifespan of C. elegans. The average lifespan of C. elegans could be fine-tuned to be as short as 15.87 ± 0.29 days with a high dose of NO, or as long as 21.13 ± 0.41 days with a low dose of NO, compared to an average life-span of 18.87 ± 0.46 days. Thus, PEG-NORM has broad potential in cell manipulation and life-span modulation and could drive the advancement of NO biology and medicine.Schematic illustration of modulating the longevity of the C. elegans by PEG-NORM nanoparticles. |
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