Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model

Mostafa Borahay, Kathleen L. Vincent, Massoud Motamedi, Ibrahim Tekedereli, Salama A. Salama, Bulent Ozpolat, Gokhan S. Kilic

Research output: Contribution to journalArticle

Abstract

Uterine leiomyomas represent a challenging problem with limited medical treatment options. The anti-tumor agent 2-methoxyestradiol (2-ME) shows promising results but its efficacy is limited by inadequate pharmacokinetics. We previously demonstrated that 2-ME nanoparticles can be successfully formulated and that they show improved in vitro anti-leiomyoma cell activity. Here, we examined the effects of the in vivo delivery of 2-ME nanoparticles in a patient-derived xenograft (PDX) leiomyoma mouse model. Patient-derived leiomyoma tumor tissues were xenografted subcutaneously in estrogen/progesterone pretreated immunodeficient NOG mice. Animals (n = 12) were treated with liposomal 2-ME nanoparticles by intra-peritoneal (IP) injection (50 mg/kg/dose, three times weekly) or control for 28 days. Tumor volume was measured weekly by calipers and prior to sacrifice by ultrasound. In addition, the expression of the cell proliferation marker Ki67 and the apoptosis marker cleaved caspase-3 in tumor tissues after treatment were measured by immunohistochemistry. Liposomal 2-ME treatment was associated with a significant tumor growth inhibition (30.5% less than controls as early as 2 weeks, p = 0.025). In addition, injections of liposomal 2-ME inhibited the expression of the proliferation marker Ki67 (55.8% reduction, p < 0.001). Furthermore, liposomal 2-ME treatment was associated with a 67.5% increase of cleaved caspase-3 expression of increase (p = 0.048). Our findings suggest that liposomal nanoparticle formulation can successfully deliver 2-ME and can be a promising therapeutic strategy for uterine leiomyoma. Further characterization of the liposomal-2ME, including pharmacokinetics, maximal tolerated dose, and safety, is needed in preclinical models prior to clinical trials.

Original languageEnglish (US)
JournalReproductive Sciences
DOIs
StateAccepted/In press - 2020

Keywords

  • 2-ME
  • 2-methoxyestradiol
  • 2ME
  • Fibroid
  • Leiomyoma
  • Liposomes
  • Nanoparticles
  • Treatment

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model'. Together they form a unique fingerprint.

  • Cite this