Intraperitoneal Nanotherapy for Metastatic Ovarian Cancer Based on SiRNA-mediated Suppression of DJ-1 Protein Combined with a Low Dose of Cisplatin

Overview

Journal Nanomedicine

Publisher Elsevier

Specialties Biomedical Engineering
Biotechnology

Date 2018 Apr 11

PMID 29635082

Citations 12

Authors

Canan Schumann

Stephanie Chan

Jess A Millar

Yuliya Bortnyak

Katherine Carey

Alex Fedchyk

Leon Wong

Tetiana Korzun

Abraham S Moses

Anna Lorenz

Delany Shea

Olena Taratula

Oleh Khalimonchuk

Oleh Taratula

Affiliations

Soon will be listed here.

Abstract

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks.

Citing Articles

Development and Perspectives: Multifunctional Nucleic Acid Nanomedicines for Treatment of Gynecological Cancers.

Korzun T, Moses A, Diba P, Sattler A, Olson B, Taratula O Small. 2023; 20(41):e2301776.

PMID: 37518857 PMC: 10827528. DOI: 10.1002/smll.202301776.

Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer.

Breusa S, Zilio S, Catania G, Bakrin N, Kryza D, Lollo G Front Oncol. 2023; 13:1125868.

PMID: 37287910 PMC: 10242058. DOI: 10.3389/fonc.2023.1125868.

An Advanced Thermal Decomposition Method to Produce Magnetic Nanoparticles with Ultrahigh Heating Efficiency for Systemic Magnetic Hyperthermia.

Demessie A, Park Y, Singh P, Moses A, Korzun T, Sabei F Small Methods. 2022; 6(12):e2200916.

PMID: 36319445 PMC: 9772135. DOI: 10.1002/smtd.202200916.

Nanoparticle-Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer-Associated Cachexia.

Korzun T, Moses A, Kim J, Patel S, Schumann C, Levasseur P Small. 2022; 18(44):e2204436.

PMID: 36098251 PMC: 9633376. DOI: 10.1002/smll.202204436.

Effects of carboplatin combined with paclitaxel-based intraperitoneal hyperthermic perfusion chemotherapy on serum levels of HE4 and DJ-1 in patients with advanced recurrent ovarian cancer.

Su X, Sun X, Kang Y, Dai Y Pak J Med Sci. 2022; 38(4Part-II):872-877.

PMID: 35634603 PMC: 9121957. DOI: 10.12669/pjms.38.4.4736.

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