Tear exosome-based PROteolysis TArgeting Chimeras nanomedicine for human immunodeficiency virus-mediated cancer treatment

Abstract

Human Immunodeficiency Virus (HIV) significantly increases the risk of various cancers due to chronic immune suppression and viral oncogenes. Traditional therapies, including antiretroviral therapy (ART), chemotherapy, and radiation, often face limitations such as drug resistance and systemic toxicity. PROteolysis TArgeting Chimeras (PROTACs) have emerged as a promising approach for targeted protein degradation, offering significant advantages over conventional treatments. However, effective delivery remains a challenge. This paper explores the innovative use of tear exosome-based delivery systems for PROTACs in treating HIV-mediated cancers. Tear exosomes, due to their natural origin, biocompatibility, and inherent targeting capabilities, present a novel and effective platform for delivering PROTACs, enhancing therapeutic specificity and reducing adverse effects. Integrating the unique properties of tear exosomes with the therapeutic potential of PROTACs could revolutionize the treatment of HIV-mediated cancers by overcoming current therapeutic challenges and improving patient outcomes.

Keywords

HIV-mediated cancer / nanomedicine / PROTACs therapy / tear exosomes / targeted protein degradation

References

[1] Yarchoan R, Uldrick TS. HIV-associated cancers and related diseases. N Engl J Med. 2018;378(11):1029-1041.

[2] Isaguliants M, Bayurova E, Avdoshina D, Kondrashova A, Chiodi F, Palefsky JM. Oncogenic effects of HIV-1 proteins, mechanisms behind. Cancers. 2021;13(2):305.

[3] Klatt NR, Chomont N, Douek DC, Deeks SG. Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev. 2013;254(1):326-342.

[4] Angeletti PC, Zhang L, Wood C. The viral etiology of AIDS-associated malignancies. Adv Pharmacol. 2008;56:509-557.

[5] da Silva SR, de Oliveira DE. HIV, EBV and KSHV: viral cooperation in the pathogenesis of human malignancies. Cancer Lett. 2011;305(2):175-185.

[6] Chen Y, Tandon I, Heelan W, Wang Y, Tang W, Hu Q. Proteolysis-targeting chimera (PROTAC) delivery system: advancing protein degraders towards clinical translation. Chem Soc Rev. 2022;51(13):5330-5350.

[7] Nalawansha DA, Crews CM. PROTACs: an emerging therapeutic modality in precision medicine. Cell Chem Biol. 2020;27(8):998-1014.

[8] Alabi SB, Crews CM. Major advances in targeted protein degradation: PROTACs, LYTACs, and MADTACs. J Biol Chem. 2021;296:100647.

[9] Cross T, Øvstebø R, Brusletto BS, et al. RNA profiles of tear fluid extracellular vesicles in patients with dry eye-related symptoms. Int J Mol Sci. 2023;24(20):15390.

[10] Sidhom K, Obi PO, Saleem A. A review of exosomal isolation methods: is size exclusion chromatography the best option? Int J Mol Sci. 2020;21(18):6466.

[11] Dhar R, Gorai S, Devi A, et al. Exosome: a megastar of future cancer personalized and precision medicine. Clin Transl Discov. 2023;3(3):e208.

[12] Morales RT, Ko J. Future of digital assays to resolve clinical of single extracellular vesicles. ACS Nano. 2022;16(8):11619-11645.

[13] Han JS, Kim SE, Jin JQ, et al. Tear-derived exosome proteins are increased in patients with thyroid eye disease. Int J Mol Sci. 2021;22(3):1115.

[14] Feng X, Peng Z, Yuan L, et al. Research progress of exosomes in pathogenesis, diagnosis, and treatment of ocular diseases. Front Bioeng Biotechnol. 2023;11:1100310.

[15] Bunggulawa EJ, Wang W, Yin T, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnol. 2018;16(1):81.

[16] Chakravarty A, Yang PL. Targeted protein degradation as an antiviral approach. Antiviral Res. 2023;210:105480.

[17] Gorgzadeh A, Nazari A, Ali Ehsan Ismaeel A, et al. A state-of-the-art review of the recent advances in exosome isolation and detection methods in viral infection. Virol J. 2024;21(1):34.

[18] Mukerjee N, Maitra S, Ghosh A, et al. Synergizing PROteolysis-TArgeting Chimeras and nanoscale exosome-based delivery mechanisms for HIV and antiviral therapeutics. ACS Appl Nano Mater. 2024;7(4):3499-3514.

RIGHTS & PERMISSIONS

2024 2024 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.