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[1] Pan BT, et al. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983 Jul;33(3):967-78.
[2] Kalluri R, et al. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977.
[3] EL Andaloussi S, et al Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013 May;12(5):347-57.
[4] Cocozza F, et al. SnapShot: Extracellular Vesicles. Cell. 2020 Jul 9;182(1):262-262.e1.
[5] Chen B, et al. Endocytic sorting and recycling require membrane phosphatidylserine asymmetry maintained by TAT-1/CHAT-1. PLoS Genet. 2010 Dec 9;6(12):e1001235.
[6] Escud¨¦ Martinez de Castilla P, et al. Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies. Adv Drug Deliv Rev. 2021 Aug;175:113801.
[7] Li Y, et al. A Novel Urine Exosomal lncRNA Assay to Improve the Detection of Prostate Cancer at Initial Biopsy: A Retrospective Multicenter Diagnostic Feasibility Study. Cancers (Basel). 2021 Aug 13;13(16):4075.
[8] Yu W, et al. Exosome-based liquid biopsies in cancer: opportunities and challenges. Ann Oncol. 2021 Apr;32(4):466-477.
[9] Heo J, et al. Exosome-Based Treatment for Atherosclerosis. Int J Mol Sci. 2022 Jan 17;23(2):1002.
[10] Shimon MB, et al. The Big Potential of Small Particles: Lipid-Based Nanoparticles and Exosomes in Vaccination. Vaccines (Basel). 2022 Jul 13;10(7):1119.
[11] Zhang M, et al. Engineered exosomes from different sources for cancer-targeted therapy. Signal Transduct Target Ther. 2023 Mar 15;8(1):124. |