Acridine Orange/exosomes Increase the Delivery and the Effectiveness of Acridine Orange in Human Melanoma Cells: A New Prototype for Theranostics of Tumors

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2017 Mar 7

PMID 28262028

Citations 52

Authors

Elisabetta Iessi

Mariantonia Logozzi

Luana Lugini

Tommaso Azzarito

Cristina Federici

Enrico Pierluigi Spugnini

Davide Mizzoni

Rossella Di Raimo

Daniela F Angelini

Luca Battistini

Serena Cecchetti

Stefano Fais

Affiliations

Soon will be listed here.

Abstract

Specifically targeted drug delivery systems with low immunogenicity and toxicity are deemed to increase efficacy of cancer chemotherapy. Acridine Orange (AO) is an acidophilic dye with a strong tumoricidal action following excitation with a light source at 466 nm. However, to date the clinical use of AO is limited by the potential side effects elicited by systemic administration. The endogenous nanocarrier exosomes have been recently introduced as a natural delivery system for therapeutic molecules. In this article, we show the outcome of the administration to human melanoma cells of AO charged Exosomes (Exo-AO), in both monolayer and spheroid models. The results showed an extended drug delivery time of Exo-AO to melanoma cells as compared to the free AO, improving the cytotoxicity of AO. This study shows that Exo-AO have a great potential for a real exploitation as a new theranostic approach against tumors based on AO delivered through the exosomes.

Citing Articles

Antioxidant Effect of a Plant-Derived Extracellular Vesicles' Mix on Human Skin Fibroblasts: Induction of a Reparative Process.

Di Raimo R, Mizzoni D, Aloi A, Pietrangelo G, Dolo V, Poppa G Antioxidants (Basel). 2024; 13(11).

PMID: 39594515 PMC: 11590891. DOI: 10.3390/antiox13111373.

Doxorubicin-loaded NK exosomes enable cytotoxicity against triple-negative breast cancer spheroids.

Hashemi Z, Ghavami M, Mohammadi F, Shokrollahi Barough M, Shokati F, Asghari S Iran J Basic Med Sci. 2024; 27(12):1604-1615.

PMID: 39539445 PMC: 11556763. DOI: 10.22038/ijbms.2024.79378.17194.

Exosome-based immunotherapy as an innovative therapeutic approach in melanoma.

Babaei S, Fadaee M, Abbasi-Kenarsari H, Shanehbandi D, Kazemi T Cell Commun Signal. 2024; 22(1):527.

PMID: 39482766 PMC: 11526674. DOI: 10.1186/s12964-024-01906-1.

Immunomodulatory effects of immune cell-derived extracellular vesicles in melanoma.

Nanru P Front Immunol. 2024; 15:1442573.

PMID: 39391320 PMC: 11464304. DOI: 10.3389/fimmu.2024.1442573.

Increased vesicular dynamics and nanoscale clustering of IL-2 after T cell activation.

Saed B, Ramseier N, Perera T, Anderson J, Burnett J, Gunasekara H Biophys J. 2024; 123(15):2343-2353.

PMID: 38532626 PMC: 11331045. DOI: 10.1016/j.bpj.2024.03.029.

References

Nakamura T, Kusuzaki K, Matsubara T, Matsumine A, Asanuma K, Satonaka H . Determination of the LD50 of acridine orange via intravenous administration in mice in preparation for clinical application to cancer therapy. In Vivo. 2014; 28(4):523-7. View

Tian Y, Li S, Song J, Ji T, Zhu M, Anderson G . A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2013; 35(7):2383-90. DOI: 10.1016/j.biomaterials.2013.11.083. View

Bailey K, Wojtkowiak J, Hashim A, Gillies R . Targeting the metabolic microenvironment of tumors. Adv Pharmacol. 2012; 65:63-107. PMC: 3796340. DOI: 10.1016/B978-0-12-397927-8.00004-X. View

Fais S . NK cell-released exosomes: Natural nanobullets against tumors. Oncoimmunology. 2013; 2(1):e22337. PMC: 3583913. DOI: 10.4161/onci.22337. View

Zuo R, Apolo A, DiGiovanna J, Parnes H, Keen C, Nanda S . Cutaneous adverse effects associated with the tyrosine-kinase inhibitor cabozantinib. JAMA Dermatol. 2014; 151(2):170-7. PMC: 6776420. DOI: 10.1001/jamadermatol.2014.2734. View

Jang S, Wientjes M, Lu D, Au J . Drug delivery and transport to solid tumors. Pharm Res. 2003; 20(9):1337-50. DOI: 10.1023/a:1025785505977. View

Zocco D, Ferruzzi P, Cappello F, Kuo W, Fais S . Extracellular vesicles as shuttles of tumor biomarkers and anti-tumor drugs. Front Oncol. 2014; 4:267. PMC: 4189328. DOI: 10.3389/fonc.2014.00267. View

Bandarchi B, Ma L, Navab R, Seth A, Rasty G . From melanocyte to metastatic malignant melanoma. Dermatol Res Pract. 2010; 2010. PMC: 2948895. DOI: 10.1155/2010/583748. View

Campanella C, Rappa F, Sciume C, Marino Gammazza A, Barone R, Bucchieri F . Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery. Cancer. 2015; 121(18):3230-9. DOI: 10.1002/cncr.29499. View

10.

Zdolsek J, Olsson G, Brunk U . Photooxidative damage to lysosomes of cultured macrophages by acridine orange. Photochem Photobiol. 1990; 51(1):67-76. DOI: 10.1111/j.1751-1097.1990.tb01685.x. View

11.

Bhatia S, Tykodi S, Thompson J . Treatment of metastatic melanoma: an overview. Oncology (Williston Park). 2009; 23(6):488-96. PMC: 2737459. View

12.

Lugini L, Federici C, Borghi M, Azzarito T, Marino M, Cesolini A . Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect. J Enzyme Inhib Med Chem. 2015; 31(4):538-45. DOI: 10.3109/14756366.2015.1046062. View

13.

Fais S, Logozzi M, Lugini L, Federici C, Azzarito T, Zarovni N . Exosomes: the ideal nanovectors for biodelivery. Biol Chem. 2012; 394(1):1-15. DOI: 10.1515/hsz-2012-0236. View

14.

Hiruma H, Katakura T, Takenami T, Igawa S, Kanoh M, Fujimura T . Vesicle disruption, plasma membrane bleb formation, and acute cell death caused by illumination with blue light in acridine orange-loaded malignant melanoma cells. J Photochem Photobiol B. 2006; 86(1):1-8. DOI: 10.1016/j.jphotobiol.2006.08.003. View

15.

Ferrari S, Perut F, Fagioli F, Brach Del Prever A, Meazza C, Parafioriti A . Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed. J Transl Med. 2013; 11:268. PMC: 3815282. DOI: 10.1186/1479-5876-11-268. View

16.

Fais S . Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism. J Intern Med. 2010; 267(5):515-25. DOI: 10.1111/j.1365-2796.2010.02225.x. View

17.

Matsubara T, Kusuzaki K, Matsumine A, Shintani K, Satonaka H, Uchida A . Acridine orange used for photodynamic therapy accumulates in malignant musculoskeletal tumors depending on pH gradient. Anticancer Res. 2006; 26(1A):187-93. View

18.

Au J, Jang S, Zheng J, Chen C, Song S, Hu L . Determinants of drug delivery and transport to solid tumors. J Control Release. 2001; 74(1-3):31-46. DOI: 10.1016/s0168-3659(01)00308-x. View

19.

Vassileva V, Allen C, Piquette-Miller M . Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer. Mol Cancer Ther. 2008; 7(3):630-7. DOI: 10.1158/1535-7163.MCT-07-2117. View

20.

Au J, Jang S, Wientjes M . Clinical aspects of drug delivery to tumors. J Control Release. 2002; 78(1-3):81-95. DOI: 10.1016/s0168-3659(01)00488-6. View