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


Erdogan O., DEMİRBOLAT G. M., Cevik O.

BIOCELL, cilt.47, sa.5, ss.1051-1063, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 47 Sayı: 5
  • Basım Tarihi: 2023
  • Doi Numarası: 10.32604/biocell.2023.028129
  • Dergi Adı: BIOCELL
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Veterinary Science Database
  • Sayfa Sayıları: ss.1051-1063
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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.