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

Thylakoid engineered M2 macrophage for sonodynamic effect promoted cell therapy of early atherosclerosis

Guanghao Wu2,§, Changwen Mu3,§, Qianru Zhao3, Yao Lei3, Ran Cheng3, Weidong Nie3, Jiamin Qu2, Yuping Dong2, Ruili Yang4( ), Haiyan Xie1( )
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Chemical Biology Center, Peking University, Beijing 100191, China
School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China
School of Life Science, Beijing Institute of Technology, Beijing 100081, China
School of Stomatology, Peking University, Beijing 100081, China

§ Guanghao Wu and Changwen Mu contributed equally to this work.

Show Author Information

Graphical Abstract

In this paper, we constructed a hybrid cell system by fusing M2 macrophages with the thylakoid membranes derived from spinach for efficient atherosclerosis treatment. The hybrid cells (TK-M2) not only inherit the natural features and functions of M2 macrophages, but also exhibit both type I and type II sonodynamic effects owing to the abundant sensitizer chlorophyll derived from thylakoid membranes.

Abstract

Atherosclerosis is the most common cause of cardiovascular diseases that contribute to the major morbidity worldwide, but still lacking of effective treatment strategy. Here, a hybrid cell is constructed for the sonodynamic effect promoted cell therapy of early atherosclerosis by fusing M2 macrophages with thylakoid (TK) membranes. After systemic administration, the obtained TK-M2 actively accumulates in the early atherosclerotic plaques, wherein M2 macrophages relieve the cholesterol accumulation and the inflammation in the foam cells. Meanwhile, the TK membranes decorated on the M2 macrophages exhibit both type I and type II sonodynamic effects under ultrasound (US) activation, inducing the direct apoptosis of foam cells. The cooperation of M2 and TK leads to significant outcome in eliminating atherosclerotic plaques without obvious side-effects, providing a new avenue for atherosclerosis treatment.

Keywords

atherosclerosisthylakoidultrasoundM2 macrophage

Electronic Supplementary Material

Download File(s)
12274_2023_6156_MOESM1_ESM.pdf (789.7 KB)

References

[1]

Libby, P.; Buring, J. E.; Badimon, L.; Hansson, G. K.; Deanfield, J.; Bittencourt, M. S.; Tokgözoğlu, L.; Lewis, E. F. Atherosclerosis. Nat. Rev. Dis. Primers 2019, 5, 56.
Crossref Google Scholar
[2]

Glass, C. K.; Witztum, J. L. Atherosclerosis. The road ahead. Cell 2001, 104, 503–516.
Crossref Google Scholar
[3]

Bjorkegren, J. L. M.; Lusis, A. J. Atherosclerosis: Recent developments. Cell 2022, 185, 1630–1645.
Crossref Google Scholar
[4]

Ungvari, Z.; Tarantini, S.; Donato, A. J.; Galvan, V.; Csiszar, A. Mechanisms of vascular aging. Circ. Res. 2018, 123, 849–867.
Crossref Google Scholar
[5]

Basatemur, G. L.; Jørgensen, H. F.; Clarke, M. C. H.; Bennett, M. R.; Mallat, Z. Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol. 2019, 16, 727–744.
Crossref Google Scholar
[6]

Koelwyn, G. J.; Corr, E. M.; Erbay, E.; Moore, K. J. Regulation of macrophage immunometabolism in atherosclerosis. Nat. Immunol. 2018, 19, 526–537.
Crossref Google Scholar
[7]

Doran, A. C.; Yurdagul, A. Jr; Tabas, I. Efferocytosis in health and disease. Nat. Rev. Immunol. 2020, 20, 254–267.
Crossref Google Scholar
[8]

Roy, P.; Orecchioni, M.; Ley, K. How the immune system shapes atherosclerosis: Roles of innate and adaptive immunity. Nat. Rev. Immunol. 2022, 22, 251–265.
Crossref Google Scholar
[9]

Yahagi, K.; Kolodgie, F. D.; Otsuka, F.; Finn, A. V.; Davis, H. R.; Joner, M.; Virmani, R. Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat. Rev. Cardiol. 2016, 13, 79–98.
Crossref Google Scholar
[10]

Badimon, L.; Vilahur, G. Thrombosis formation on atherosclerotic lesions and plaque rupture. J. Intern. Med. 2014, 276, 618–632.
Crossref Google Scholar
[11]

Luo, X.; Lv, Y.; Bai, X. X.; Qi, J. Y.; Weng, X. Z.; Liu, S. Y.; Bao, X. Y.; Jia, H. B.; Yu, B. Plaque erosion: A distinctive pathological mechanism of acute coronary syndrome. Front. Cardiovasc. Med. 2021, 8, 711453.
Crossref Google Scholar
[12]

Lobatto, M. E.; Fuster, V.; Fayad, Z. A.; Mulder, W. J. M. Perspectives and opportunities for nanomedicine in the management of atherosclerosis. Nat. Rev. Drug Discovery 2011, 10, 835–852.
Crossref Google Scholar
[13]

Hu, P. P.; Luo, S. X.; Fan, X. Q.; Li, D.; Tong, X. Y. Macrophage-targeted nanomedicine for the diagnosis and management of atherosclerosis. Front. Pharmacol. 2022, 13, 1000316.
Crossref Google Scholar
[14]

Libby, P.; Ridker, P. M.; Hansson, G. K. Progress and challenges in translating the biology of atherosclerosis. Nature 2011, 473, 317–325.
Crossref Google Scholar
[15]

Smith, B. R.; Edelman, E. R. Nanomedicines for cardiovascular disease. Nat. Cardiovasc. Res. 2023, 2, 351–367.
Crossref Google Scholar
[16]

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
[17]

Zhang, S.; Liu, Y.; Cao, Y.; Zhang, S. T.; Sun, J.; Wang, Y. H.; Song, S. Y.; Zhang, H. J. Targeting the microenvironment of vulnerable atherosclerotic plaques: An emerging diagnosis and therapy strategy for atherosclerosis. Adv. Mater. 2022, 34, 2110660.
Crossref Google Scholar
[18]

Xu, H.; Li, S.; Liu, Y. S. Nanoparticles in the diagnosis and treatment of vascular aging and related diseases. Signal Transduction Targeted Ther. 2022, 7, 231.
Crossref Google Scholar
[19]

ao, W.; Yurdagul, A. Jr.; Kong, N.; Li, W. L.; Wang, X. B.; Doran, A. C.; Feng, C.; Wang, J. Q.; Islam, M. A.; Farokhzad, O. C. et al. siRNA nanoparticles targeting CaMKIIγ in lesional macrophages improve atherosclerotic plaque stability in mice. Sci. Transl. Med. 2020, 23, eaay1063.
Crossref Google Scholar
[20]

Huang, X. G.; Liu, C.; Kong, N.; Xiao, Y. F.; Yurdagul, A. Jr; Tabas, I.; Tao, W. Synthesis of siRNA nanoparticles to silence plaque-destabilizing gene in atherosclerotic lesional macrophages. Nat. Protoc. 2022, 17, 748–780.
Crossref Google Scholar
[21]

Singh, A. P.; Biswas, A.; Shukla, A.; Maiti, P. Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles. Signal Transduction Targeted Ther. 2019, 4, 33.
Crossref Google Scholar
[22]

Zhang, X. W.; Centurion, F.; Misra, A.; Patel, S.; Gu, Z. Molecularly targeted nanomedicine enabled by inorganic nanoparticles for atherosclerosis diagnosis and treatment. Adv. Drug Delivery Rev. 2023, 194, 114709.
Crossref Google Scholar
[23]

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
[24]

Chen, Y. X.; Qin, D. T.; Zou, J. H.; Li, X. B.; Guo, X. D.; Tang, Y.; Liu, C.; Chen, W.; Kong, N.; Zhang, C. Y. et al. Living leukocyte-based drug delivery systems. Adv. Mater. 2023, 35, 2207787.
Crossref Google Scholar
[25]

Chan, C. K. W.; Zhang, L.; Cheng, C. K.; Yang, H. R.; Huang, Y.; Tian, X. Y.; Choi, C. H. J. Recent advances in managing atherosclerosis via nanomedicine. Small 2018, 14, 1702793.
Crossref Google Scholar
[26]

Mulder, W. J. M.; Jaffer, F. A.; Fayad, Z. A.; Nahrendorf, M. Imaging and nanomedicine in inflammatory atherosclerosis. Sci. Transl. Med. 2014, 6, 239sr1.
Crossref Google Scholar
[27]

Bouchareychas, L.; Duong, P.; Covarrubias, S.; Alsop, E.; Phu, T. A.; Chung, A.; Gomes, M.; Wong, D.; Meechoovet, B.; Capili, A. et al. Macrophage exosomes resolve atherosclerosis by regulating hematopoiesis and inflammation via MicroRNA cargo. Cell Rep. 2020, 32, 107881.
Crossref Google Scholar
[28]

Yang, W. Z.; Yin, R. H.; Zhu, X. Y.; Yang, S. N.; Wang, J.; Zhou, Z. F.; Pan, X. D.; Ma, A. J. Mesenchymal stem-cell-derived exosomal miR-145 inhibits atherosclerosis by targeting JAM-A. Mol. Ther. -Nucleic Acids 2021, 23, 119–131.
Crossref Google Scholar
[29]

Lázaro-Ibáñez, E.; Faruqu, F. N.; Saleh, A. F.; Silva, A. M.; Wang, J. T. W.; Rak, J.; Al-Jamal, K. T.; Dekker, N. Selection of fluorescent, bioluminescent, and radioactive tracers to accurately reflect extracellular vesicle biodistribution in vivo. ACS Nano 2021, 15, 3212–3227.
Crossref Google Scholar
[30]

Zhang, X.; Zhang, H. B.; Gu, J. M.; Zhang, J. Y.; Shi, H.; Qian, H.; Wang, D. Q.; Xu, W. R.; Pan, J. M.; Santos, H. A. Engineered extracellular vesicles for cancer therapy. Adv. Mater. 2021, 33, 2005709.
Crossref Google Scholar
[31]

Liu, J. J.; Zhou, B.; Guo, Y. L.; Zhang, A. M.; Yang, K.; He, Y.; Wang, J. B.; Cheng, Y. S.; Cui, D. X. SR-A-targeted nanoplatform for sequential photothermal/photodynamic ablation of activated macrophages to alleviate atherosclerosis. ACS Appl. Mater. Interfaces 2021, 13, 29349–29362.
Crossref Google Scholar
[32]

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
[33]

Ouyang, J.; Xie, A.; Zhou, J.; Liu, R. C.; Wang, L. Q.; Liu, H. J.; Kong, N.; Tao, W. Minimally invasive nanomedicine: Nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging. Chem. Soc. Rev. 2022, 51, 4996–5041.
Crossref Google Scholar
[34]

Meng, N.; Gong, Y.; Zhang, J. F.; Mu, X.; Song, Z. M.; Feng, R. L.; Zhang, H. A novel curcumin-loaded nanoparticle restricts atherosclerosis development and promotes plaques stability in apolipoprotein E deficient mice. J. Biomater. Appl. 2019, 33, 946–954.
Crossref Google Scholar
[35]

Bi, Y.; Chen, J. X.; Hu, F.; Liu, J.; Li, M.; Zhao, L. M2 macrophages as a potential target for antiatherosclerosis treatment. Neural. Plast. 2019, 2019, 6724903.
Crossref Google Scholar
[36]

Wang, H.; Yang, Y.; Sun, X.; Tian, F.; Guo, S. Y.; Wang, W.; Tian, Z.; Jin, H.; Zhang, Z. G.; Tian, Y. Sonodynamic therapy-induced foam cells apoptosis activates the phagocytic PPARγ-LXRα-ABCA1/ABCG1 pathway and promotes cholesterol efflux in advanced plaque. Theranostics 2018, 8, 4969–4984.
Crossref Google Scholar
[37]

Ouyang, J.; Wang, L. Q.; Chen, W. S.; Zeng, K.; Han, Y. J.; Xu, Y.; Xu, Q. F.; Deng, L.; Liu, Y. N. Biomimetic nanothylakoids for efficient imaging-guided photodynamic therapy for cancer. Chem. Commun. 2018, 54, 3468–3471.
Crossref Google Scholar
[38]

Lei, Y.; Zhao, H. L.; Wu, Y. Z.; Huang, L. L.; Nie, W. D.; Liu, H. L.; Wu, G. H.; Pang, D. W.; Xie, H. Y. Phytochemical natural killer cells reprogram tumor microenvironment for potent immunotherapy of solid tumors. Biomaterials 2022, 287, 121635.
Crossref Google Scholar
[39]

Zhuang, W. R.; Wang, Y. F.; Lei, Y.; Zuo, L. P.; Jiang, A. Q.; Wu, G. H.; Nie, W. D.; Huang, L. L.; Xie, H. Y. Phytochemical engineered bacterial outer membrane vesicles for photodynamic effects promoted immunotherapy. Nano Lett. 2022, 22, 4491–4500.
Crossref Google Scholar
[40]

Liu, H. L.; Lei, Y.; Nie, W. D.; Zhao, H. L.; Wu, Y. Z.; Zuo, L. P.; Wu, G. H.; Yang, R. L.; Xie, H. Y. Immunomodulatory hybrid bio-nanovesicle for self-promoted photodynamic therapy. Nano Res. 2022, 15, 4233–4242.
Crossref Google Scholar
[41]

Tang, J. N.; Su, T.; Huang, K.; Dinh, P. U.; Wang, Z. G.; Vandergriff, A.; Hensley, M. T.; Cores, J.; Allen, T.; Li, T. S. et al. Targeted repair of heart injury by stem cells fused with platelet nanovesicles. Nat. Biomed. Eng. 2018, 2, 17–26.
Crossref Google Scholar
[42]

Liu, W. L.; Zou, M. Z.; Liu, T.; Zeng, J. Y.; Li, X.; Yu, W. Y.; Li, C. X.; Ye, J. J.; Song, W.; Feng, J. et al. Cytomembrane nanovaccines show therapeutic effects by mimicking tumor cells and antigen presenting cells. Nat. Commun. 2019, 10, 3199.
Crossref Google Scholar
[43]

Ci, T. Y.; Li, H. J.; Chen, G. J.; Wang, Z. J.; Wang, J. Q.; Abdou, P.; Tu, Y. M.; Dotti, G.; Gu, Z. Cryo-shocked cancer cells for targeted drug delivery and vaccination. Sci. Adv. 2020, 6, eabc3013.
Crossref Google Scholar
[44]

Whitman, S. C. A practical approach to using mice in atherosclerosis research. Clin. Biochem. Rev. 2004, 25, 81–93.
Google Scholar
[45]

Sheptovitsky, Y. G.; Brudvig, G. W. Catalase-free photosystem II: The O2-evolving complex does not dismutate hydrogen peroxide. Biochemistry 1998, 37, 5052–5059.
Crossref Google Scholar
[46]

Biswas, S. K.; Mantovani, A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm. Nat. Immunol. 2010, 11, 889–896.
Crossref Google Scholar
[47]

Shapouri-Moghaddam, A.; Mohammadian, S.; Vazini, H.; Taghadosi, M.; Esmaeili, S. A.; Mardani, F.; Seifi, B.; Mohammadi, A.; Afshari, J. T.; Sahebkar, A. Macrophage plasticity, polarization, and function in health and disease. J. Cell. Physiol. 2018, 233, 6425–6440.
Crossref Google Scholar
[48]

Tabas, I.; Lichtman, A. H. Monocyte-macrophages and T cells in atherosclerosis. Immunity 2017, 47, 621–634.
Crossref Google Scholar
[49]

Barrett, T. J. Macrophages in atherosclerosis regression. Arterioscler., Thromb., Vasc. Biol. 2020, 40, 20–33.
Crossref Google Scholar
[50]

Kitamoto, S.; Egashira, K.; Ichiki, T.; Han, X. B.; McCurdy, S.; Sakuda, S.; Sunagawa, K.; Boisvert, W. A. Chitinase inhibition promotes atherosclerosis in hyperlipidemic mice. Am. J. Pathol. 2013, 183, 313–325.
Crossref Google Scholar
[51]

Jahn, D.; Verkam Biochem p, E.; Söll, D. Glutamyl-transfer RNA: A precursor of heme and chlorophyll biosynthesis. Trends. Sci. 1992, 17, 215–218.
Crossref Google Scholar
[52]

Reinbothe, C.; El Bakkouri, M.; Buhr, F.; Muraki, N.; Nomata, J.; Kurisu, G.; Fujita, Y.; Reinbothe, S. Chlorophyll biosynthesis: Spotlight on protochlorophyllide reduction. Trends Plant Sci. 2010, 15, 614–624.
Crossref Google Scholar
[53]

Zhang, Z. J.; Kang, M. M.; Tan, H.; Song, N.; Li, M.; Xiao, P. H.; Yan, D. Y.; Zhang, L. P.; Wang, D.; Tang, B. Z. The fast-growing field of photo-driven theranostics based on aggregation-induced emission. Chem. Soc. Rev. 2022, 51, 1983–2030.
Crossref Google Scholar
[54]

Wu, W. B.; Mao, D.; Xu, S. D.; Kenry; Hu, F.; Li, X. Q.; Kong, D. L.; Liu, B. Polymerization-enhanced photosensitization. Chem 2018, 4, 1937–1951.
Crossref Google Scholar
Nano Research
Volume 17 Issue 4,
April 2024
Pages 2919-2928
DOI: 10.1007/s12274-023-6156-2
Cite this article:
Wu G, Mu C, Zhao Q, et al. Thylakoid engineered M2 macrophage for sonodynamic effect promoted cell therapy of early atherosclerosis. Nano Research, 2024, 17(4): 2919-2928. https://doi.org/10.1007/s12274-023-6156-2
Topics:
Nanobiotechnology

628

Views

2

Crossref

0

Web of Science

3

Scopus

0

CSCD

Altmetrics
Received: 28 June 2023
Revised: 31 August 2023
Accepted: 04 September 2023
Published: 28 September 2023
© Tsinghua University Press 2023
Return