Extracellular Vesicles Deliver Sodium Iodide Symporter Protein and Promote Cancer Cell Radioiodine Therapy

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jul 1

PMID 35778503

Authors

Jin Hee Lee

Kyung-Ho Jung

Kim Mina

Kyung-Han Lee

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are a promising carrier for various cargos with antitumor effects, but their capacity to transfer the ability to transport radioiodine for cancer theranostics remains unexplored. Herein, we tested the hypothesis that EVs can be loaded with the sodium iodide symporter (NIS) protein and efficiently deliver the payload to recipient cancer cells to facilitate radioiodine uptake. The results revealed that donor cells either transduced with an adenoviral vector for transient expression or engineered for stable overexpression secreted EVs that contained substantial amounts of NIS protein but not NIS mRNA. Huh7 liver cancer cells treated with EVs secreted from each of the donor cell types showed significantly increased plasma membrane NIS protein, indicating efficient payload delivery. Furthermore, intact function of the delivered NIS protein was confirmed by significantly increased radioiodine transport in recipient cancer cells that peaked at 48 h. Importantly, NIS protein delivered by EVs significantly enhanced the antitumor effects of I radiotherapy. These results reveal that EVs are a promising vehicle to deliver NIS protein to cancer cells in sufficient amounts for radioiodine-based theranostics.

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References

Cabeza L, Perazzoli G, Pena M, Cepero A, Luque C, Melguizo C . Cancer therapy based on extracellular vesicles as drug delivery vehicles. J Control Release. 2020; 327:296-315. DOI: 10.1016/j.jconrel.2020.08.018. View

Hadla M, Palazzolo S, Corona G, Caligiuri I, Canzonieri V, Toffoli G . Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models. Nanomedicine (Lond). 2016; 11(18):2431-41. DOI: 10.2217/nnm-2016-0154. View

Davis L, Smith A, Aldridge M, Foulkes J, Peet C, Wan S . Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics. J Pers Med. 2020; 10(4). PMC: 7711590. DOI: 10.3390/jpm10040174. View

Batrakova E, Kim M . Development and regulation of exosome-based therapy products. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2016; 8(5):744-57. DOI: 10.1002/wnan.1395. View

Logozzi M, De Milito A, Lugini L, Borghi M, Calabro L, Spada M . High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One. 2009; 4(4):e5219. PMC: 2667632. DOI: 10.1371/journal.pone.0005219. View

Kamerkar S, LeBleu V, Sugimoto H, Yang S, Ruivo C, Melo S . Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017; 546(7659):498-503. PMC: 5538883. DOI: 10.1038/nature22341. View

Melo S, Sugimoto H, OConnell J, Kato N, Villanueva A, Vidal A . Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014; 26(5):707-21. PMC: 4254633. DOI: 10.1016/j.ccell.2014.09.005. View

Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee J, Lotvall J . Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9(6):654-9. DOI: 10.1038/ncb1596. View

Srivastava A, Amreddy N, Razaq M, Towner R, Zhao Y, Ahmed R . Exosomes as Theranostics for Lung Cancer. Adv Cancer Res. 2018; 139:1-33. PMC: 6548197. DOI: 10.1016/bs.acr.2018.04.001. View

10.

Smyth T, Kullberg M, Malik N, Smith-Jones P, Graner M, Anchordoquy T . Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J Control Release. 2014; 199:145-55. PMC: 4441346. DOI: 10.1016/j.jconrel.2014.12.013. View

11.

Pegtel D, Gould S . Exosomes. Annu Rev Biochem. 2019; 88:487-514. DOI: 10.1146/annurev-biochem-013118-111902. View

12.

Sterzenbach U, Putz U, Low L, Silke J, Tan S, Howitt J . Engineered Exosomes as Vehicles for Biologically Active Proteins. Mol Ther. 2017; 25(6):1269-1278. PMC: 5474961. DOI: 10.1016/j.ymthe.2017.03.030. View

13.

Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K . ExoCarta: A Web-Based Compendium of Exosomal Cargo. J Mol Biol. 2015; 428(4):688-692. PMC: 4783248. DOI: 10.1016/j.jmb.2015.09.019. View

14.

Fan J, Wei Q, Koay E, Liu Y, Ning B, Bernard P . Chemoresistance Transmission via Exosome-Mediated EphA2 Transfer in Pancreatic Cancer. Theranostics. 2019; 8(21):5986-5994. PMC: 6299429. DOI: 10.7150/thno.26650. View

15.

Vader P, Mol E, Pasterkamp G, Schiffelers R . Extracellular vesicles for drug delivery. Adv Drug Deliv Rev. 2016; 106(Pt A):148-156. DOI: 10.1016/j.addr.2016.02.006. View

16.

Yang M, Du Q, Varley P, Goswami J, Liang Z, Wang R . Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response. Br J Cancer. 2017; 118(1):62-71. PMC: 5765230. DOI: 10.1038/bjc.2017.389. View

17.

Riedel C, Levy O, Carrasco N . Post-transcriptional regulation of the sodium/iodide symporter by thyrotropin. J Biol Chem. 2001; 276(24):21458-63. DOI: 10.1074/jbc.M100561200. View

18.

White-Gilbertson S, Kurtz D, Voelkel-Johnson C . The role of protein synthesis in cell cycling and cancer. Mol Oncol. 2009; 3(5-6):402-8. PMC: 2784195. DOI: 10.1016/j.molonc.2009.05.003. View

19.

Lorenc T, Chrzanowski J, Olejarz W . Current Perspectives on Clinical Use of Exosomes as a Personalized Contrast Media and Theranostics. Cancers (Basel). 2020; 12(11). PMC: 7698051. DOI: 10.3390/cancers12113386. View

20.

Boland A, Ricard M, Opolon P, Bidart J, Yeh P, Filetti S . Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy. Cancer Res. 2000; 60(13):3484-92. View