Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

doi:10.4251/wjgo.v16.i9.4006

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World Journal of Gastrointestinal Oncology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastrointest Oncol. Sep 15, 2024; 16(9): 4006-4013
Published online Sep 15, 2024. doi: 10.4251/wjgo.v16.i9.4006

Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

Zu-Gui Tang, Tie-Mei Chen, Yi Lu, Zhe Wang, Xi-Cheng Wang, Yi Kong

Zu-Gui Tang, Tie-Mei Chen, Zhe Wang, Xi-Cheng Wang, Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, Guangdong Province, China

Zu-Gui Tang, Yi Kong, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518000, Guangdong Province, China

Yi Lu, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong Province, China

Co-corresponding authors: Xi-Cheng Wang and Yi Kong.

Author contributions: Wang XC and Kong Y designed the study and were responsible for the work, and they are the co-corresponding authors of this manuscript. Tang ZG, Chen TM, and Lu Y performed the research; Wang Z analyzed the data; Kong Y wrote the manuscript. All authors have read and approved the final manuscript.

Supported by Guangdong Basic and Applied Basic Research Foundation, No. 2019A1515011609; the Project of Educational Commission of Guangdong Province of China, No. 2018KQNCX124; and Guangzhou Science and Technology Key Point Project, No. 202103000041.

Institutional review board statement: Our study exclusively involves in vitro cell experiments and does not involve human subjects or animals. Therefore, it does not require ethical approval.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Corresponding author: Yi Kong, PhD, Associate Professor, Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, No. 1068 Xueyuan Avenue, Nanshan District, Shenzhen 518000, Guangdong Province, China. yi.kong@siat.ac.cn

Received: May 25, 2024
Revised: June 29, 2024
Accepted: July 26, 2024
Published online: September 15, 2024
Processing time: 106 Days and 22 Hours

Abstract

BACKGROUND

Pancreatic cancer remains one of the most lethal malignancies, and has limited effective treatment. Gemcitabine (GEM), a chemotherapeutic agent, is commonly used for clinical treatment of pancreatic cancer, but it has characteristics of low drug delivery efficiency and significant side effects. The study tested the hypothesis that human bone marrow mesenchymal stem cell (MSC)-derived exosomes loaded with GEM (Exo-GEM) would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.

AIM

To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.

METHODS

Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis. Exo-GEM through electroporation, sonication, or incubation, and the loading efficiency was evaluated. The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.

RESULTS

The isolated exosomes had an average size of 76.7 nm. The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation. The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02 μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells. Moreover, Exo-GEM enhanced the frequency of GEM-induced apoptosis in both cell lines.

CONCLUSION

Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis, offering a promising drug delivery system for improving therapeutic outcomes.

Keywords: Mesenchymal stem cells; Exosomes; Extracellular vesicles; Gemcitabine; Pancreatic cancer; Drug delivery

Core Tip: This study investigates the utilization of exosomes derived from human bone marrow mesenchymal stem cells as a novel system to deliver gemcitabine (GEM) for the treatment of pancreatic cancer. Through the optimization of GEM loading into exosomes, the results indicate that exosomes loaded with GEM (Exo-GEM) have a potent cytotoxicity against pancreatic cancer cells by enhancing their apoptosis in vitro. These findings underscore the potential of Exo-GEM as a more efficient and targeted therapeutic approach for enhancing therapeutic efficacy in patients with pancreatic cancer.