AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Selenopeptide nanomedicine ameliorates atherosclerosis by reducing monocyte adhesions and inflammations

Zhen Luo1,2,§, Yuxing Jiang1,3,§, Zimo Liu1,4,§, Lamei Guo1,5,§, Li Zhang1,5, Hongtao Rong3, Zhongyu Duan2, Hongwen Liang6, Aili Zhang7, Lei Wang1,4, Yu Yi1,4( ), Hao Wang1,4( )
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China
Tianjin Medical University General Hospital, Tianjin 300052, China
University of Chinese Academy of Sciences, Beijing 100049, China
School of Environmental Science and Safety Engineering, Tianjin University of Technology, Tianjin 300384, China
College of Pharmacy, Chongqing Medical University, Chongqing 400016, China
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China

§ Zhen Luo, Yuxing Jiang, Zimo Liu, and Lamei Guo contributed equally to this work.

Show Author Information

Graphical Abstract

An atherosclerotic plaque-targeted selenopeptide nanomedicine is developed for atherosclerosis management by reducing monocyte adhesions and macrophage inflammations. Local oxidation of the selenopeptide not only reduces oxidation stress and triggers drug release, but also generates amphiphilic seleno-metabolites in situ that form micelles for P-selectin blockage to inhibit monocyte adhesions and inflammations in synergy.

Abstract

Atherosclerosis is an inflammatory disease that may cause severe heart disease and stroke. Current pharmacotherapy for atherosclerosis shows limited benefits. In the progression of atherosclerosis, monocyte adhesions and inflammatory macrophages play vital roles. However, precise regulations of inflammatory immune microenvironments in pathological tissues remain challenging. Here, we report an atherosclerotic plaque-targeted selenopeptide nanomedicine for inhibiting atherosclerosis progression by reducing monocyte adhesions and inflammation of macrophages. The targeted nanomedicine has 2.2-fold enhancement in atherosclerotic lesion accumulation. The oxidation-responsibility of selenopeptide enables eliminations of reactive oxygen species and specific release of anti-inflammatory drugs, thereby reducing inflammation responses of macrophages. Notably, we find the oxidative metabolite of selenopeptide, octadecyl selenite, can bind to P-selectin in a high affinity with a dissociation constant of 1.5 μM. This in situ generated active seleno-species further inhibit monocyte adhesions for anti-inflammation in synergy. With local regulations of monocyte adhesions and inflammations, the selenopeptide nanomedicine achieves 2.6-fold improvement in atherosclerotic plaque inhibition compared with simvastatin in the atherosclerosis mouse model. Meanwhile, the selenopeptide nanomedicine also displays excellent biological safety in both mice and rhesus monkeys. This study provides a safe and effective platform for regulating inflammatory immune microenvironments for inflammatory diseases such as atherosclerosis.

Keywords

selenopeptideself-assemblyatherosclerosismonocyte adhesionanti-inflammation

Electronic Supplementary Material

Download File(s)
6547_ESM.pdf (2.8 MB)

References

[1]

Libby, P. The changing landscape of atherosclerosis. Nature 2021, 592, 524–533.
Crossref Google Scholar
[2]

Hansson, G. K. Inflammation, atherosclerosis, and coronary artery disease. N. Engl. J. Med. 2005, 352, 1685–1695.
Crossref Google Scholar
[3]

Tombling, B. J.; Zhang, Y. H.; Huang, Y. H.; Craik, D. J.; Wang, C. K. The emerging landscape of peptide-based inhibitors of PCSK9. Atherosclerosis 2021, 330, 52–60.
Crossref Google Scholar
[4]

Engelen, S. E.; Robinson, A. J. B.; Zurke, Y. X.; Monaco, C. Therapeutic strategies targeting inflammation and immunity in atherosclerosis: How to proceed. Nat. Rev. Cardiol. 2022, 19, 522–542.
Crossref Google Scholar
[5]

Chen, W.; Schilperoort, M.; Cao, Y. H.; Shi, J. J.; Tabas, I.; Tao, W. Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis. Nat. Rev. Cardiol. 2022, 19, 228–249.
Crossref Google Scholar
[6]

Wang, Q.; Jing, H. S.; Lin, J.; Wu, Z. H.; Tian, Y.; Gong, K.; Guo, Q. Q.; Yang, X. P.; Wang, L. T.; Li, Z. J. et al. Programmed prodrug breaking the feedback regulation of P-selectin in plaque inflammation for atherosclerotic therapy. Biomaterials 2022, 288, 121705.
Crossref Google Scholar
[7]

Hu, Q. Q.; Fang, Z. Y.; Ge, J. B.; Li, H. Nanotechnology for cardiovascular diseases. Innovation 2022, 3, 100214.
Google Scholar
[8]

Smith, B. R.; Edelman, E. R. Nanomedicines for cardiovascular disease. Nat. Cardiovasc. Res. 2023, 2, 351–367.
Crossref Google Scholar
[9]

Gao, C.; Huang, Q. X.; Liu, C. H.; Kwong, C. H. T.; Yue, L. D.; Wan, J. B.; Lee, S. M. Y.; Wang, R. B. Treatment of atherosclerosis by macrophage-biomimetic nanoparticles via targeted pharmacotherapy and sequestration of proinflammatory cytokines. Nat. Commun. 2020, 11, 2622.
Crossref Google Scholar
[10]

Wu, G. H.; Zhang, J. F.; Zhao, Q. R.; Zhuang, W. R.; Ding, J. J.; Zhang, C.; Gao, H. J.; Pang, D. W.; Pu, K. Y.; Xie, H. Y. Molecularly engineered macrophage-derived exosomes with inflammation tropism and intrinsic heme biosynthesis for atherosclerosis treatment. Angew. Chem., Int. Ed. 2020, 59, 4068–4074.
Crossref Google Scholar
[11]

Hu, R. Z.; Dai, C.; Dong, C. H.; Ding, L.; Huang, H.; Chen, Y.; Zhang, B. Living macrophage-delivered tetrapod PdH nanoenzyme for targeted atherosclerosis management by ROS scavenging, hydrogen anti-inflammation, and autophagy activation. ACS Nano 2022, 16, 15959–15976.
Crossref Google Scholar
[12]

Wu, G. H.; Mu, C. W.; Zhao, Q. R.; Lei, Y.; Cheng, R.; Nie, W. D.; Qu, J. M.; Dong, Y. P.; Yang, R. L.; Xie, H. Y. Thylakoid engineered M2 macrophage for sonodynamic effect promoted cell therapy of early atherosclerosis. Nano Res. 2024, 17, 2919–2928.
Crossref Google Scholar
[13]

Guo, M. R.; He, Z. S.; Jin, Z. H.; Huang, L. J.; Yuan, J. M.; Qin, S. G.; Wang, X. C.; Cao, L. L.; Song, X. R. Oral nanoparticles containing naringenin suppress atherosclerotic progression by targeting delivery to plaque macrophages. Nano Res. 2023, 16, 925–937.
Crossref Google Scholar
[14]

Gao, M. Z.; Tang, M. P.; Ho, W.; Teng, Y. L.; Chen, Q. J.; Bu, L.; Xu, X. Y.; Zhang, X. Q. Modulating plaque inflammation via targeted mRNA nanoparticles for the treatment of atherosclerosis. ACS Nano 2023, 17, 17721–17739.
Crossref Google Scholar
[15]

Flores, A. M.; Hosseini-Nassab, N.; Jarr, K. U.; Ye, J. Q.; Zhu, X. J.; Wirka, R.; Koh, A. L.; Tsantilas, P.; Wang, Y.; Nanda, V. et al. Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis. Nat. Nanotechnol. 2020, 15, 154–161.
Crossref Google Scholar
[16]

Soehnlein, O.; Libby, P. Targeting inflammation in atherosclerosis-from experimental insights to the clinic. Nat. Rev. Drug Discov. 2021, 20, 589–610.
Crossref Google Scholar
[17]

Rayman, M. P. Selenium and human health. Lancet 2012, 379, 1256–1268.
Crossref Google Scholar
[18]

Reich, H. J.; Hondal, R. J. Why nature chose selenium. ACS Chem. Biol. 2016, 11, 821–841.
Crossref Google Scholar
[19]

Wang, Y.; Wu, J.; Tang, S. H.; Yang, J. R.; Ye, C. L.; Chen, J.; Lei, Y. P.; Wang, D. S. Synergistic Fe-Se atom pairs as bifunctional oxygen electrocatalysts boost low-temperature rechargeable Zn-air battery. Angew. Chem., Int. Ed. 2023, 62, e202219191.
Crossref Google Scholar
[20]
He, C. W.; Liu, C.; Pan, S. J.; Tan, Y. Z.; Guan, J.; Xu, H. P. Polyurethane with β-selenocarbonyl structure enabling the combination of plastic degradation and waste upcycling. Angew. Chem., Int. Ed., in press, DOI: 10.1002/anie.202317558.
[21]

Shi, D. L.; Liu, W. W.; Gao, Y.; Li, X. M.; Huang, Y. Y.; Li, X. K.; James, T. D.; Guo, Y.; Li, J. Photoactivatable senolysis with single-cell resolution delays aging. Nat. Aging 2023, 3, 297–312.
Crossref Google Scholar
[22]

Sun, J. M.; Du, Z. Z.; Liu, Y. H.; Ai, W.; Wang, K.; Wang, T.; Du, H. F.; Liu, L.; Huang, W. State-of-the-art and future challenges in high energy lithium-selenium batteries. Adv. Mater. 2021, 33, 2003845.
Crossref Google Scholar
[23]

Winther, K. H.; Rayman, M. P.; Bonnema, S. J.; Hegedus, L. Selenium in thyroid disorders - essential knowledge for clinicians. Nat. Rev. Endocrinol. 2020, 16, 165–176.
Crossref Google Scholar
[24]

Li, T. Y.; Xu, H. P. Selenium-containing nanomaterials for cancer treatment. Cell Rep. Phys. Sci. 2020, 1, 100111.
Crossref Google Scholar
[25]

Huang, Y. Y.; Su, E. Z.; Ren, J. S.; Qu, X. G. The recent biological applications of selenium-based nanomaterials. Nano Today 2021, 38, 101205.
Crossref Google Scholar
[26]

Li, T. Y.; Pan, S. J.; Gao, S. Q.; Xiang, W. T.; Sun, C. X.; Cao, W.; Xu, H. P. Diselenide-pemetrexed assemblies for combined cancer immuno-, radio-, and chemotherapies. Angew. Chem., Int. Ed. 2020, 59, 2700–2704.
Crossref Google Scholar
[27]

Zhang, L.; Sun, C. X.; Tan, Y. Z.; Xu, H. P. Selenium-sulfur-doped carbon dots with thioredoxin reductase activity. CCS Chem. 2022, 4, 2239–2248.
Crossref Google Scholar
[28]

Zhu, L. W.; Chan, L.; Wang, J. P.; Chen, M. K.; Cai, F.; Tian, Y.; Ma, L.; Chen, T. F. Selenium-engineered bottom-up-synthesized lanthanide coordination nanoframeworks as efficiency X-ray-responsive radiosensitizers. Nano Res. 2023, 16, 5169–5175.
Crossref Google Scholar
[29]

Chen, M. K.; Cao, W. Q.; Wang, J. P.; Cai, F.; Zhu, L. W.; Ma, L.; Chen, T. F. Selenium atom-polarization effect determines TrxR-specific recognition of metallodrugs. J. Am. Chem. Soc. 2022, 144, 20825–20833.
Crossref Google Scholar
[30]
Xianyu, B. R.; Pan, S. J.; Gao, S. Q.; Xu, H. P.; Li, T. Y. Selenium-containing nanocomplexes achieve dual immune checkpoint blockade for NK cell reinvigoration. Small, in press, DOI: 10.1002/smll.202306225.
[31]

Yang, H.; Liu, C.; Wu, Y. J.; Yuan, M.; Huang, J. R.; Xia, Y. H.; Ling, Q. J.; Hoffmann, P. R.; Huang, Z.; Chen, T. F. Atherosclerotic plaque-targeted nanotherapeutics ameliorates atherogenesis by blocking macrophage-driven inflammation. Nano Today 2022, 42, 101351.
Crossref Google Scholar
[32]

Yin, M. D.; Lin, J. F.; Yang, M. Y.; Li, C.; Wu, P. Y.; Zou, J. J.; Jiang, Y. J.; Shao, J. W. Platelet membrane-cloaked selenium/ginsenoside Rb1 nanosystem as biomimetic reactor for atherosclerosis therapy. Colloids Surf. B: Biointerfaces 2022, 214, 112464.
Crossref Google Scholar
[33]

Xu, J. Q.; Xu, J. C.; Shi, T. F.; Zhang, Y. L.; Chen, F. M.; Yang, C.; Guo, X. J.; Liu, G. N.; Shao, D.; Leong, K. W. et al. Probiotic-inspired nanomedicine restores intestinal homeostasis in colitis by regulating redox balance, immune responses, and the gut microbiome. Adv. Mater. 2023, 35, 2207890.
Crossref Google Scholar
[34]

Xiong, Z. S.; Lin, H.; Li, H.; Zou, B. H.; Xie, B.; Yu, Y. Z.; He, L. Z.; Chen, T. F. Chiral selenium nanotherapeutics regulates selenoproteins to attenuate glucocorticoid-induced osteoporosis. Adv. Funct. Mater. 2023, 33, 2212970.
Crossref Google Scholar
[35]

Ouyang, J.; Deng, B.; Zou, B. H.; Li, Y. J.; Bu, Q. Y.; Tian, Y.; Chen, M. K.; Chen, W.; Kong, N.; Chen, T. F. et al. Oral hydrogel microbeads-mediated in situ synthesis of selenoproteins for regulating intestinal immunity and microbiota. J. Am. Chem. Soc. 2023, 145, 12193–12205.
Crossref Google Scholar
[36]

Zhang, H. J.; Gao, L. Y.; Sui, M. L.; Wang, J. J.; Wang, Y. P.; Xuan, X. Y.; Zhang, Z. Z.; Zhu, L.; Hou, L. The “two-pronged” nanosystem to precisely improve lipid metabolism and inflammatory microenvironment for atherosclerotic plaque stabilization. Nano Res. 2023, 16, 2706–2718.
Crossref Google Scholar
[37]

Xu, J. Q.; Chu, T. J.; Yu, T. T.; Li, N. S.; Wang, C. L.; Li, C.; Zhang, Y. L.; Meng, H.; Nie, G. J. Design of diselenide-bridged hyaluronic acid nano-antioxidant for efficient ros scavenging to relieve colitis. ACS Nano 2022, 16, 13037–13048.
Crossref Google Scholar
[38]

Xie, B.; Zeng, D. L.; Yang, M. J.; Tang, Z. Y.; He, L. Z.; Chen, T. F. Translational selenium nanoparticles to attenuate allergic dermatitis through Nrf2-Keap1-driven activation of selenoproteins. ACS Nano 2023, 17, 14053–14068.
Crossref Google Scholar
[39]

Chagri, S.; Ng, D. Y. W.; Weil, T. Designing bioresponsive nanomaterials for intracellular self-assembly. Nat. Rev. Chem. 2022, 6, 320–338.
Crossref Google Scholar
[40]

Kim, J.; Lee, S.; Kim, Y.; Choi, M.; Lee, I.; Kim, E.; Yoon, C. G.; Pu, K. Y.; Kang, H.; Kim, J. S. In situ self-assembly for cancer therapy and imaging. Nat. Rev. Mater. 2023, 8, 710–725.
Crossref Google Scholar
[41]
Yi, Y.; An, H. W.; Wang, H. Intelligent biomaterialomics: Molecular design, manufacturing, and biomedical applications. Adv. Mater., in press, DOI: 10.1002/adma.202305099.
[42]
Mamuti, M.; Zheng, R.; An, H. W.; Wang, H. In vivo self-assembled nanomedicine. Nano Today 2021 , 36, 101036.
[43]

Zhang, X. Y.; Wang, J. X.; Zhang, Y.; Yang, Z. M.; Gao, J.; Gu, Z. Synthesizing biomaterials in living organisms. Chem. Soc. Rev. 2023, 52, 8126–8164.
Crossref Google Scholar
[44]

Guo, L. M.; Yang, J. J.; Wang, H.; Yi, Y. Multistage self-assembled nanomaterials for cancer immunotherapy. Molecules 2023, 28, 7750.
Crossref Google Scholar
[45]

Wei, Z. Y.; Yi, Y.; Luo, Z.; Gong, X. Y.; Jiang, Y. X.; Hou, D. Y.; Zhang, L.; Liu, Z. M.; Wang, M. D.; Wang, J. et al. Selenopeptide nanomedicine activates natural killer cells for enhanced tumor chemoimmunotherapy. Adv. Mater. 2022, 34, 2108167.
Crossref Google Scholar
[46]

Li, Y. B.; Han, J. Y.; Jiang, W.; Wang, J. Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells. Mol. Biol. Rep. 2011, 38, 2301–2306.
Crossref Google Scholar
[47]

Wang, P. F.; Gong, Q. J.; Hu, J. B.; Li, X.; Zhang, X. J. Reactive oxygen species (ROS)-responsive prodrugs, probes, and theranostic prodrugs: Applications in the ROS-related diseases. J. Med. Chem. 2021, 64, 298–325.
Crossref Google Scholar
[48]

He, J. H.; Zhang, W. L.; Zhou, X. J.; Xu, F. F.; Zou, J. H.; Zhang, Q. Q.; Zhao, Y.; He, H. L.; Yang, H.; Liu, J. P. Reactive oxygen species (ROS)-responsive size-reducible nanoassemblies for deeper atherosclerotic plaque penetration and enhanced macrophage-targeted drug delivery. Bioact. Mater. 2023, 19, 115–126.
Crossref Google Scholar
[49]

Ali, S. T.; Karamat, S.; Kóňa, J.; Fabian, W. M. F. Theoretical prediction of p Ka values of seleninic, selenenic, sulfinic, and carboxylic acids by quantum-chemical methods. J. Phys. Chem. A 2010, 114, 12470–12478.
Crossref Google Scholar
[50]

Madabeni, A.; Zucchelli, S.; Nogara, P. A.; Rocha, J. B. T.; Orian, L. In the chalcogenoxide elimination panorama: Systematic insight into a key reaction. J. Org. Chem. 2022, 87, 11766–11775.
Crossref Google Scholar
[51]

Liu, C.; Shen, M. C.; Tan, W. L. W.; Chen, I. Y.; Liu, Y.; Yu, X.; Yang, H. X.; Zhang, A.; Liu, Y. X.; Zhao, M. T. et al. Statins improve endothelial function via suppression of epigenetic-driven endmt. Nat. Cardiovasc. Res. 2023, 2, 467–485.
Crossref Google Scholar
[52]

Smith, B. A. H.; Bertozzi, C. R. The clinical impact of glycobiology: Targeting selectins, siglecs and mammalian glycans. Nat. Rev. Drug Discov. 2021, 20, 217–243.
Crossref Google Scholar
[53]

Hong, Y.; Hu, Y.; Sun, Y. A.; Shi, J. Q.; Xu, J. High-fat diet caused renal damage in ApoE-/- mice via the activation of RAGE-mediated inflammation. Toxicol. Res. 2021, 10, 1171–1176.
Crossref Google Scholar
[54]
Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H. et al. Gaussian 16, Rev. C.01; Gaussian, Inc.: Wallingford, CT, USA, 2016.
Nano Research
Volume 17 Issue 7,
July 2024
Pages 6332-6341
DOI: 10.1007/s12274-024-6547-z
Cite this article:
Luo Z, Jiang Y, Liu Z, et al. Selenopeptide nanomedicine ameliorates atherosclerosis by reducing monocyte adhesions and inflammations. Nano Research, 2024, 17(7): 6332-6341. https://doi.org/10.1007/s12274-024-6547-z
Topics:
Nano biology

675

Views

3

Crossref

1

Web of Science

3

Scopus

0

CSCD

Altmetrics
Received: 11 January 2024
Revised: 03 February 2024
Accepted: 03 February 2024
Published: 13 March 2024
© Tsinghua University Press 2024
Return