Harnessing exosomes for targeted therapy: strategy and application
Exosomes, nanoscopic extracellular vesicles produced by cells, are pivotal in mediating intracellular communication by transporting nucleic acids, proteins, lipids, and other bioactive molecules, thereby influencing physiological and pathological states. Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications. Despite their potential, the clinical utility of exosomes is hampered by challenges such as limited storage stability, yield, purity, and targeting efficiency. This review focuses on exosomes as targeted therapeutic agents, examining their biogenesis, classification, isolation, and characterisation, while also addressing the current limitations in yield, purity, and targeting. We delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.
Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.
1.Ren, X.; Chen, X.; Geng, Z.; Su, J. Bone-targeted biomaterials: strategies and applications. Chem Eng J. 2022, 446, 137133.
2. Liu, J.; Zhang, Y.; Wu, Y.; Li, G.; Ji, N.; Han, R.; Tang, H.; Liu, X.; Liu, H.; Wang, C.; Cui, J.; Song, P.; Jing, Y.; Chen, X.; Su, J. Delivery of m7G methylated Runx2 mRNA by bone-targeted lipid nanoparticle promotes osteoblastic bone formation in senile osteoporosis. Nano Today. 2024, 54, 102074.
3. Ren, X.; Sun, Z.; Ma, X.; Wang, Y.; Cui, X.; Yi, Z.; Sun, X.; Guo, B.; Li, X. Alginate-mediated mineralization for ultrafine hydroxyapatite hybrid nanoparticles. Langmuir. 2018, 34, 6797-6805.
4. Wang, J.; Li, X.; Wang, S.; Cui, J.; Ren, X.; Su, J. Bone-targeted exosomes: strategies and applications. Adv Healthc Mater. 2023, 12, e2203361.
5. Huang, L.; Wu, E.; Liao, J.; Wei, Z.; Wang, J.; Chen, Z. Research advances of engineered exosomes as drug delivery carrier. ACS Omega. 2023, 8, 43374-43387.
6. Moloudizargari, M.; Asghari, M. H.; Goel, A. The therapeutic triad of extracellular vesicles: As drug targets, as drugs, and as drug carriers. Biochem Pharmacol. 2021, 192, 114714.
7. Lu, M.; Huang, Y. Bioinspired exosome-like therapeutics and delivery nanoplatforms. Biomaterials. 2020, 242, 119925.
8. Gao, S.; Yang, X.; Xu, J.; Qiu, N.; Zhai, G. Nanotechnology for boosting cancer immunotherapy and remodeling tumor microenvironment: the horizons in cancer treatment. ACS Nano. 2021, 15, 12567-12603.
9. He, J.; Ren, W.; Wang, W.; Han, W.; Jiang, L.; Zhang, D.; Guo, M. Exosomal targeting and its potential clinical application. Drug Deliv Transl Res. 2022, 12, 2385-2402.
10. Jiang, Y.; Li, J.; Xue, X.; Yin, Z.; Xu, K.; Su, J. Engineered extracellular vesicles for bone therapy. Nano Today. 2022, 44, 101487.
11. Yáñez-Mó, M.; Siljander, P. R.; Andreu, Z.; Zavec, A. B.; Borràs, F. E.; Buzas, E. I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; Colás, E.; Cordeiro-da Silva, A.; Fais, S.; Falcon-Perez, J. M.; Ghobrial, I. M.; Giebel, B.; Gimona, M.; Graner, M.; Gursel, I.; Gursel, M.; Heegaard, N. H.; Hendrix, A.; Kierulf, P.; Kokubun, K.; Kosanovic, M.; Kralj-Iglic, V.; Krämer-Albers, E. M.; Laitinen, S.; Lässer, C.; Lener, T.; Ligeti, E.; Linē, A.; Lipps, G.; Llorente, A.; Lötvall, J.; Manček-Keber, M.; Marcilla, A.; Mittelbrunn, M.; Nazarenko, I.; Nolte-’t Hoen, E. N.; Nyman, T. A.; O’Driscoll, L.; Olivan, M.; Oliveira, C.; Pállinger, É.; Del Portillo, H. A.; Reventós, J.; Rigau, M.; Rohde, E.; Sammar, M.; Sánchez-Madrid, F.; Santarém, N.; Schallmoser, K.; Ostenfeld, M. S.; Stoorvogel, W.; Stukelj, R.; Van der Grein, S. G.; Vasconcelos, M. H.; Wauben, M. H.; De Wever, O. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015, 4, 27066.
12. Saad, M. H.; Badierah, R.; Redwan, E. M.; El-Fakharany, E. M. A comprehensive insight into the role of exosomes in viral infection: dual faces bearing different functions. Pharmaceutics. 2021, 13, 1405.
13. Gurung, S.; Perocheau, D.; Touramanidou, L.; Baruteau, J. The exosome journey: from biogenesis to uptake and intracellular signalling. Cell Commun Signal. 2021, 19, 47.
14. Isaac, R.; Reis, F. C. G.; Ying, W.; Olefsky, J. M. Exosomes as mediators of intercellular crosstalk in metabolism. Cell Metab. 2021, 33, 1744-1762.
15. Sun, Z.; Wu, Y.; Gao, F.; Li, H.; Wang, C.; Du, L.; Dong, L.; Jiang, Y. In situ detection of exosomal RNAs for cancer diagnosis. Acta Biomater. 2023, 155, 80-98.
16. Liu, S. L.; Sun, P.; Li, Y.; Liu, S. S.; Lu, Y. Exosomes as critical mediators of cell-to-cell communication in cancer pathogenesis and their potential clinical application. Transl Cancer Res. 2019, 8, 298-311.
17. Spanos, M.; Gokulnath, P.; Chatterjee, E.; Li, G.; Varrias, D.; Das, S. Expanding the horizon of EV-RNAs: lncRNAs in EVs as biomarkers for disease pathways. Extracell Vesicle. 2023, 2, 100025.
18. Han, R.; Wu, Y.; Han, Y.; Liu, X.; Liu, H.; Su, J. Engineered plant extracellular vesicles for autoimmune diseases therapy. Nano Res. 2024, 17, 2857-2873.
19. Abels, E. R.; Breakefield, X. O. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016, 36, 301-312.
20. Janas, A. M.; Sapoń, K.; Janas, T.; Stowell, M. H.; Janas, T. Exosomes and other extracellular vesicles in neural cells and neurodegenerative diseases. Biochim Biophys Acta. 2016, 1858, 1139-1151.
21. Xu, M.; Ji, J.; Jin, D.; Wu, Y.; Wu, T.; Lin, R.; Zhu, S.; Jiang, F.; Ji, Y.; Bao, B.; Li, M.; Xu, W.; Xiao, M. The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): intercellular shuttles and implications in human diseases. Genes Dis. 2023, 10, 1894-1907.
22. Liu, C.; Liu, D.; Wang, S.; Gan, L.; Yang, X.; Ma, C. Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion. J Extracell Vesicles. 2023, 12, e12356.
23. Kalluri, R.; LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science. 2020, 367, eaau6977.
24. Wang, Y.; Guo, M.; Lin, D.; Liang, D.; Zhao, L.; Zhao, R.; Wang, Y. Docetaxel-loaded exosomes for targeting non-small cell lung cancer: preparation and evaluation in vitro and in vivo. Drug Deliv. 2021, 28, 1510-1523.
25. Montecalvo, A.; Larregina, A. T.; Shufesky, W. J.; Stolz, D. B.; Sullivan, M. L.; Karlsson, J. M.; Baty, C. J.; Gibson, G. A.; Erdos, G.; Wang, Z.; Milosevic, J.; Tkacheva, O. A.; Divito, S. J.; Jordan, R.; Lyons-Weiler, J.; Watkins, S. C.; Morelli, A. E. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood. 2012, 119, 756-766.
26. Zhu, L.; Sun, H. T.; Wang, S.; Huang, S. L.; Zheng, Y.; Wang, C. Q.; Hu, B. Y.; Qin, W.; Zou, T. T.; Fu, Y.; Shen, X. T.; Zhu, W. W.; Geng, Y.; Lu, L.; Jia, H. L.; Qin, L. X.; Dong, Q. Z. Isolation and characterization of exosomes for cancer research. J Hematol Oncol. 2020, 13, 152.
27. Nolte-’t Hoen, E. N.; Buschow, S. I.; Anderton, S. M.; Stoorvogel, W.; Wauben, M. H. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood. 2009, 113, 1977-1981.
28. Xie, Y.; Zhang, H.; Li, W.; Deng, Y.; Munegowda, M. A.; Chibbar, R.; Qureshi, M.; Xiang, J. Dendritic cells recruit T cell exosomes via exosomal LFA-1 leading to inhibition of CD8+ CTL responses through downregulation of peptide/MHC class I and Fas ligand-mediated cytotoxicity. J Immunol. 2010, 185, 5268-5278.
29. Saunderson, S. C.; Dunn, A. C.; Crocker, P. R.; McLellan, A. D. CD169 mediates the capture of exosomes in spleen and lymph node. Blood. 2014, 123, 208-216.
30. Enomoto, Y.; Li, P.; Jenkins, L. M.; Anastasakis, D.; Lyons, G. C.; Hafner, M.; Leonard, W. J. Cytokine-enhanced cytolytic activity of exosomes from NK cells. Cancer Gene Ther. 2022, 29, 734-749.
31. Ma, Y. S.; Wu, T. M.; Ling, C. C.; Yu, F.; Zhang, J.; Cao, P. S.; Gu, L. P.; Wang, H. M.; Xu, H.; Li, L.; Wu, Z. J.; Wang, G. R.; Li, W.; Lin, Q. L.; Liu, J. B.; Fu, D. M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B. Mol Ther Oncolytics. 2021, 20, 484-498.
32. Chen, H.; Wang, L.; Zeng, X.; Schwarz, H.; Nanda, H. S.; Peng, X.; Zhou, Y. Exosomes, a new star for targeted delivery. Front Cell Dev Biol. 2021, 9, 751079.
33. Liang, Y.; Duan, L.; Lu, J.; Xia, J. Engineering exosomes for targeted drug delivery. Theranostics. 2021, 11, 3183-3195.
34. Andreu, Z.; Yáñez-Mó, M. Tetraspanins in extracellular vesicle formation and function. Front Immunol. 2014, 5, 442.
35. Simhadri, V. R.; Reiners, K. S.; Hansen, H. P.; Topolar, D.; Simhadri, V. L.; Nohroudi, K.; Kufer, T. A.; Engert, A.; Pogge von Strandmann, E. Dendritic cells release HLA-B-associated transcript-3 positive exosomes to regulate natural killer function. PLoS One. 2008, 3, e3377.
36. Chistiakov, D. A.; Killingsworth, M. C.; Myasoedova, V. A.; Orekhov, A. N.; Bobryshev, Y. V. CD68/macrosialin: not just a histochemical marker. Lab Invest. 2017, 97, 4-13.
37. Wilke, S.; Krausze, J.; Büssow, K. Crystal structure of the conserved domain of the DC lysosomal associated membrane protein: implications for the lysosomal glycocalyx. BMC Biol. 2012, 10, 62.
38. El-Andaloussi, S.; Lee, Y.; Lakhal-Littleton, S.; Li, J.; Seow, Y.; Gardiner, C.; Alvarez-Erviti, L.; Sargent, I. L.; Wood, M. J. Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc. 2012, 7, 2112-2126.
39. Yang, J.; Zhang, X.; Chen, X.; Wang, L.; Yang, G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids. 2017, 7, 278-287.
40. Liu, Y.; Li, D.; Liu, Z.; Zhou, Y.; Chu, D.; Li, X.; Jiang, X.; Hou, D.; Chen, X.; Chen, Y.; Yang, Z.; Jin, L.; Jiang, W.; Tian, C.; Zhou, G.; Zen, K.; Zhang, J.; Zhang, Y.; Li, J.; Zhang, C. Y. Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse. Sci Rep. 2015, 5, 17543.
41. Kim, G.; Kim, M.; Lee, Y.; Byun, J. W.; Hwang, D. W.; Lee, M. Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes. J Control Release. 2020, 317, 273-281.
42. Kim, G.; Lee, Y.; Ha, J.; Han, S.; Lee, M. Engineering exosomes for pulmonary delivery of peptides and drugs to inflammatory lung cells by inhalation. J Control Release. 2021, 330, 684-695.
43. Tian, Y.; Li, S.; Song, J.; Ji, T.; Zhu, M.; Anderson, G. J.; Wei, J.; Nie, G. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014, 35, 2383-2390.
44. Bellavia, D.; Raimondo, S.; Calabrese, G.; Forte, S.; Cristaldi, M.; Patinella, A.; Memeo, L.; Manno, M.; Raccosta, S.; Diana, P.; Cirrincione, G.; Giavaresi, G.; Monteleone, F.; Fontana, S.; De Leo, G.; Alessandro, R. Interleukin 3-receptor targeted exosomes inhibit in vitro and in vivo chronic myelogenous leukemia cell growth. Theranostics. 2017, 7, 1333-1345.
45. Li, Z.; Zhou, X.; Wei, M.; Gao, X.; Zhao, L.; Shi, R.; Sun, W.; Duan, Y; Yang, G.; Yuan, L. In vitro and in vivo RNA inhibition by CD9-HuR functionalized exosomes encapsulated with miRNA or CRISPR/dCas9. Nano Lett. 2019, 19, 19-28.
46. Shi, X.; Cheng, Q.; Hou, T.; Han, M.; Smbatyan, G.; Lang, J. E.; Epstein, A. L.; Lenz, H. J.; Zhang, Y. Genetically engineered cell-derived nanoparticles for targeted breast cancer immunotherapy. Mol Ther. 2020, 28, 536-547.
47. Molavipordanjani, S.; Khodashenas, S.; Abedi, S. M.; Moghadam, M. F.; Mardanshahi, A.; Hosseinimehr, S. J. (99m)Tc-radiolabeled HER2 targeted exosome for tumor imaging. Eur J Pharm Sci. 2020, 148, 105312.
48. Kooijmans, S. A.; Aleza, C. G.; Roffler, S. R.; van Solinge, W. W.; Vader, P.; Schiffelers, R. M. Display of GPI-anchored anti-EGFR nanobodies on extracellular vesicles promotes tumour cell targeting. J Extracell Vesicles. 2016, 5, 31053.
49. Sun, S.; Liu, H.; Hu, Y.; Wang, Y.; Zhao, M.; Yuan, Y.; Han, Y.; Jing, Y.; Cui, J.; Ren, X.; Chen, X.; Su, J. Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle. Bioact Mater. 2023, 20, 166-178.
50. Gao, X.; Ran, N.; Dong, X.; Zuo, B.; Yang, R.; Zhou, Q.; Moulton, H. M.; Seow, Y.; Yin, H. Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy. Sci Transl Med. 2018, 10, eaat0195.
51. Yerneni, S. S.; Lathwal, S.; Shrestha, P.; Shirwan, H.; Matyjaszewski, K.; Weiss, L.; Yolcu, E. S.; Campbell, P. G.; Das, S. R. Rapid on-demand extracellular vesicle augmentation with versatile oligonucleotide tethers. ACS Nano. 2019, 13, 10555-10565.
52. Luo, Z. W.; Li, F. X.; Liu, Y. W.; Rao, S. S.; Yin, H.; Huang, J.; Chen, C. Y.; Hu, Y.; Zhang, Y.; Tan, Y. J.; Yuan, L. Q.; Chen, T. H.; Liu, H. M.; Cao, J.; Liu, Z. Z.; Wang, Z. X.; Xie, H. Aptamer-functionalized exosomes from bone marrow stromal cells target bone to promote bone regeneration. Nanoscale. 2019, 11, 20884-20892.
53. Wang, J.; Li, W.; Lu, Z.; Zhang, L.; Hu, Y.; Li, Q.; Du, W.; Feng, X.; Jia, H.; Liu, B. F. The use of RGD-engineered exosomes for enhanced targeting ability and synergistic therapy toward angiogenesis. Nanoscale. 2017, 9, 15598-15605.
54. Liu, S. Radiolabeled cyclic RGD peptides as integrin alpha(v)beta(3)-targeted radiotracers: maximizing binding affinity via bivalency. Bioconjug Chem. 2009, 20, 2199-2213.
55. Avgoulas, D. I.; Tasioulis, K. S.; Papi, R. M.; Pantazaki, A. A. Therapeutic and diagnostic potential of exosomes as drug delivery systems in brain cancer. Pharmaceutics. 2023, 15, 1439.
56. Li, S.; Wu, Y.; Ding, F.; Yang, J.; Li, J.; Gao, X.; Zhang, C.; Feng, J. Engineering macrophage-derived exosomes for targeted chemotherapy of triple-negative breast cancer. Nanoscale. 2020, 12, 10854-10862.
57. Ohno, S.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T.; Gotoh, N.; Kuroda, M. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013, 21, 185-191.
58. Ji, N.; Wang, F.; Wang, M.; Zhang, W.; Liu, H.; Su, J. Engineered bacterial extracellular vesicles for central nervous system diseases. J Control Release. 2023, 364, 46-60.
59. Mentkowski, K. I.; Lang, J. K. Exosomes engineered to express a cardiomyocyte binding peptide demonstrate improved cardiac retention in vivo. Sci Rep. 2019, 9, 10041.
60. Sun, J.; Yin, Z.; Wang, X.; Su, J. Exosome-laden hydrogels: a novel cell-free strategy for in-situ bone tissue regeneration. Front Bioeng Biotechnol. 2022, 10, 866208.
61. Ferreira, D.; Moreira, J. N.; Rodrigues, L. R. New advances in exosome-based targeted drug delivery systems. Crit Rev Oncol Hematol. 2022, 172, 103628.
62. Kim, H.; Jang, H.; Cho, H.; Choi, J.; Hwang, K. Y.; Choi, Y.; Kim, S. H.; Yang, Y. Recent advances in exosome-based drug delivery for cancer therapy. Cancers (Basel). 2021, 13, 4435.
63. Li, X.; Corbett, A. L.; Taatizadeh, E.; Tasnim, N.; Little, J. P.; Garnis, C.; Daugaard, M.; Guns, E.; Hoorfar, M.; Li, I. T. S. Challenges and opportunities in exosome research-perspectives from biology, engineering, and cancer therapy. APL Bioeng. 2019, 3, 011503.
64. Ren, X.; Yi, Z.; Sun, Z.; Ma, X.; Chen, G.; Chen, Z.; Li, X. Natural polysaccharide-incorporated hydroxyapatite as size-changeable, nuclear-targeted nanocarrier for efficient cancer therapy. Biomater Sci. 2020, 8, 5390-5401.
65. Jiang, L.; Gu, Y.; Du, Y.; Liu, J. Exosomes: diagnostic biomarkers and therapeutic delivery vehicles for cancer. Mol Pharm. 2019, 16, 3333-3349.
66. Qi, H.; Liu, C.; Long, L.; Ren, Y.; Zhang, S.; Chang, X.; Qian, X.; Jia, H.; Zhao, J.; Sun, J.; Hou, X.; Yuan, X.; Kang, C. Blood exosomes endowed with magnetic and targeting properties for cancer therapy. ACS Nano. 2016, 10, 3323-3333.
67. Jiang, L.; Gu, Y.; Du, Y.; Tang, X.; Wu, X.; Liu, J. Engineering exosomes endowed with targeted delivery of triptolide for malignant melanoma therapy. ACS Appl Mater Interfaces. 2021, 13, 42411-42428.
68. Zou, J.; Shi, M.; Liu, X.; Jin, C.; Xing, X.; Qiu, L.; Tan, W. Aptamer-functionalized exosomes: elucidating the cellular uptake mechanism and the potential for cancer-targeted chemotherapy. Anal Chem. 2019, 91, 2425-2430.
69. Zhang, M.; Hu, S.; Liu, L.; Dang, P.; Liu, Y.; Sun, Z.; Qiao, B.; Wang, C. Engineered exosomes from different sources for cancer-targeted therapy. Signal Transduct Target Ther. 2023, 8, 124.
70. Kim, H.; Yun, N.; Mun, D.; Kang, J. Y.; Lee, S. H.; Park, H.; Park, H.; Joung, B. Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes. Biochem Biophys Res Commun. 2018, 499, 803-808.
71. Wang, J.; Liu, Y.; Liu, Y.; Huang, H.; Roy, S.; Song, Z.; Guo, B. Recent advances in nanomedicines for imaging and therapy of myocardial ischemia-reperfusion injury. J Control Release. 2023, 353, 563-590.
72. Wang, X.; Chen, Y.; Zhao, Z.; Meng, Q.; Yu, Y.; Sun, J.; Yang, Z.; Chen, Y.; Li, J.; Ma, T.; Liu, H.; Li, Z.; Yang, J.; Shen, Z. Engineered exosomes with ischemic myocardium-targeting peptide for targeted therapy in myocardial infarction. J Am Heart Assoc. 2018, 7, e008737.
73. Sen, S.; Xavier, J.; Kumar, N.; Ahmad, M. Z.; Ranjan, O. P. Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives. 3 Biotech. 2023, 13, 101.
74. Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M. J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011, 29, 341-345.
75. Liu, H.; Zhang, H.; Wang, S.; Cui, J.; Weng, W.; Liu, X.; Tang, H.; Hu, Y.; Li, X.; Zhang, K.; Zhou, F.; Jing, Y.; Su, J. Bone-targeted bioengineered bacterial extracellular vesicles delivering siRNA to ameliorate osteoporosis. Compos B Eng. 2023, 255, 110610.
76. Liu, H.; Zhang, Q.; Wang, S.; Weng, W.; Jing, Y.; Su, J. Bacterial extracellular vesicles as bioactive nanocarriers for drug delivery: Advances and perspectives. Bioact Mater. 2022, 14, 169-181.
77. Meng, F.; Yin, Z.; Ren, X.; Geng, Z.; Su, J. Construction of local drug delivery system on titanium-based implants to improve osseointegration. Pharmaceutics. 2022, 14, 1069.
78. Zhang, Y.; Li, G.; Wang, J.; Zhou, F.; Ren, X.; Su, J. Small joint organoids 3D bioprinting: construction strategy and application. Small. 2023, e2302506.
79. Song, H.; Li, X.; Zhao, Z.; Qian, J.; Wang, Y.; Cui, J.; Weng, W.; Cao, L.; Chen, X.; Hu, Y.; Su, J. Reversal of osteoporotic activity by endothelial cell-secreted bone targeting and biocompatible exosomes. Nano Lett. 2019, 19, 3040-3048.
80. Hu, Y.; Li, X.; Zhang, Q.; Gu, Z.; Luo, Y.; Guo, J.; Wang, X.; Jing, Y.; Chen, X.; Su, J. Exosome-guided bone targeted delivery of Antagomir-188 as an anabolic therapy for bone loss. Bioact Mater. 2021, 6, 2905-2913.
81. Cui, Y.; Guo, Y.; Kong, L.; Shi, J.; Liu, P.; Li, R.; Geng, Y.; Gao, W.; Zhang, Z.; Fu, D. A bone-targeted engineered exosome platform delivering siRNA to treat osteoporosis. Bioact Mater. 2022, 10, 207-221.
82. Wang, Y.; Yao, J.; Cai, L.; Liu, T.; Wang, X.; Zhang, Y.; Zhou, Z.; Li, T.; Liu, M.; Lai, R.; Liu, X. Bone-targeted extracellular vesicles from mesenchymal stem cells for osteoporosis therapy. Int J Nanomedicine. 2020, 15, 7967-7977.
