Targeted reversal of multidrug resistance in ovarian cancer cells using exosome-encapsulated tetramethylpyrazine

Abstract

The objective of the present study was to develop exosomes (eXos) encapsulating tetramethylpyrazine (TMP) for the reversal of drug resistance in ovarian cancer therapy. Human a2780 cells were incubated with TMP for 48 h. Purified TMP-primed eXos (eXos-TMP) were isolated through ultracentrifugation. The developed eXos-TMP were characterized using techniques such as transmission electron microscopy, nanoparticle tracking analysis, Fluorescence microscopy and western blotting. Subsequently, MTT, western blotting and flow cytometry assays were performed to evaluate the biological effects in drug-resistant a2780T cells. The results demonstrated that the incorporation of TMP into eXos exhibited an anti-ovarian cancer effect and markedly enhanced the antitumor efficacy of paclitaxel (PTX). Furthermore, it was identified that the ability of EXO-TMP to reverse cell resistance was associated with the downregulation of multidrug resistance protein 1, multidrug resistant-associated protein 1 and glutathione S-transferase Pi protein expression. Flow cytometry analysis revealed that eXo-TMP induced apoptosis in drug-resistant cells and enhanced the apoptotic effect when combined with PTX. eXos are naturally sourced, exhibit excellent biocompatibility and enable precise drug delivery to target sites, thereby reducing toxic side effects. overall, eXo-TMP exhibited direct targeting capabilities towards a2780T cells and effectively reduced their drug resistance. eXos-TMP provide a novel and effective drug delivery pathway for reversing drug resistance in ovarian cancer.