Open Access

ARTICLE

Raloxifene-loaded and aptamer-bonded exosomes induce autophagic and apoptotic death in HeLa cells by enhancing the lysosomotropic effect

by OMER ERDOGAN¹, GULEN MELIKE DEMIRBOLAT², OZGE CEVIK^1,*

1 Department of Medical Biochemistry, School of Medicine, Aydin Adnan Menderes University, Aydin, 09010, Turkey
2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Acibadem Mehmet Ali Aydinlar University, Istanbul, 34758, Turkey

* Corresponding Author: OZGE CEVIK. Email:

BIOCELL 2023, 47(5), 1051-1063. https://doi.org/10.32604/biocell.2023.028129

Received 01 December 2022; Accepted 28 February 2023; Issue published 10 April 2023

Abstract

Background: Raloxifene, a selective estrogen receptor modulator, is also known to be a lysosomotropic agent. The bioavailability of raloxifene is around 2% due to extensive hepatic transport. Exosomes are nanosized vesicles that are naturally released from cells. Method: In this study, exosomes released from HeLa cervical cancer cells were loaded with raloxifene to increase its bioavailability, and an aptamer was attached to the exosome membrane for targeting only HeLa cells. Characterization of exosomes isolated from HeLa cells was performed by transmission electron microscopy, zeta sizer, and western blotting. In addition, the cytotoxic, apoptotic, autophagic, and lysosomotropic effects of the prepared Exo-Apt-Ral formulation on HeLa cervical cancer cells were investigated. Results: According to zeta analysis, the sizes of the empty exosome and Exo-Apt-Ral formulation were measured as 66 ± 12 and 120 ± 21 nm, respectively. There was a rise in the lysosomal permeability of HeLa cells after the Exo-Apt-Ral application. In addition, both apoptotic and autophagic death mechanisms were triggered in HeLa cells after the Exo-Apt-Ral application. Conclusion: This study showed that raloxifene functionalized by loading into aptamer-bound exosomes can be a new targeted drug carrier system for cervical cancer.

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