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Research Article

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

Guanghao Wu2,§Changwen Mu3,§Qianru Zhao3Yao Lei3Ran Cheng3Weidong Nie3Jiamin Qu2Yuping Dong2Ruili 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.

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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.

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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.

[2]

Glass, C. K.; Witztum, J. L. Atherosclerosis. The road ahead. Cell 2001, 104, 503–516.

[3]

Bjorkegren, J. L. M.; Lusis, A. J. Atherosclerosis: Recent developments. Cell 2022, 185, 1630–1645.

[4]

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

[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.

[6]

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

[7]

Doran, A. C.; Yurdagul, A. Jr; Tabas, I. Efferocytosis in health and disease. Nat. Rev. Immunol. 2020, 20, 254–267.

[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.

[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.

[10]

Badimon, L.; Vilahur, G. Thrombosis formation on atherosclerotic lesions and plaque rupture. J. Intern. Med. 2014, 276, 618–632.

[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.

[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.

[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.

[14]

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

[15]

Smith, B. R.; Edelman, E. R. Nanomedicines for cardiovascular disease. Nat. Cardiovasc. Res. 2023, 2, 351–367.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[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.

[44]

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

[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.

[46]

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

[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.

[48]

Tabas, I.; Lichtman, A. H. Monocyte-macrophages and T cells in atherosclerosis. Immunity 2017, 47, 621–634.

[49]

Barrett, T. J. Macrophages in atherosclerosis regression. Arterioscler., Thromb., Vasc. Biol. 2020, 40, 20–33.

[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.

[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.

[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.

[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.

[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.

Nano Research
Pages 2919-2928
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
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Received: 28 June 2023
Revised: 31 August 2023
Accepted: 04 September 2023
Published: 28 September 2023
© Tsinghua University Press 2023
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