Kim HJ, Lee DS, Park JH, Hong HE, Choi HJ, Kim OH, Kim SJ. Exosome-based strategy against colon cancer using small interfering RNA-loaded vesicles targeting soluble a proliferation-inducing ligand. World J Stem Cells 2024; 16(11): 956-973 [PMID: 39619877 DOI: 10.4252/wjsc.v16.i11.956]
Corresponding Author of This Article
Say-June Kim, Doctor, PhD, Professor, Surgeon, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, South Korea. sayjunekim@catholic.ac.kr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Nov 26, 2024; 16(11): 956-973 Published online Nov 26, 2024. doi: 10.4252/wjsc.v16.i11.956
Exosome-based strategy against colon cancer using small interfering RNA-loaded vesicles targeting soluble a proliferation-inducing ligand
Hyung-Jin Kim, Do Sang Lee, Jung Hyun Park, Ha-Eun Hong, Ho Joong Choi, Ok-Hee Kim, Say-June Kim
Hyung-Jin Kim, Jung Hyun Park, Department of Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, South Korea
Do Sang Lee, Ho Joong Choi, Say-June Kim, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Do Sang Lee, Jung Hyun Park, Ha-Eun Hong, Ok-Hee Kim, Say-June Kim, Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
Ha-Eun Hong, Ok-Hee Kim, Translational Research Team, Surginex Co., Ltd., Seoul 06591, South Korea
Co-corresponding authors: Ok-Hee Kim and Say-June Kim.
Author contributions: Lee DS, Park JH, and Choi HJ participated in the analysis and interpretation of data; Hong HE and Kim OH performed various experiments and participated in the analysis of data; All authors read and approved the manuscript. Kim SJ and Kim OH contributed equally as co-corresponding authors, whereby Kim SJ led the study design, data interpretation, and manuscript preparation and Kim OH co-led the experimental design, data analysis, and interpretation.
Supported by the National Research Foundation of Korea, No. NRF-2018R1D1A1B07047144.
Institutional animal care and use committee statement: The animal experiments adhered to the guidelines of the Institute for Laboratory Animal Research, the Catholic University of Korea (IRB No: CUMC-2020-0119-05).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Dataset available upon reasonable request from the corresponding author at sayjunekim@catholic.ac.kr.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Say-June Kim, Doctor, PhD, Professor, Surgeon, Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, South Korea. sayjunekim@catholic.ac.kr
Received: June 7, 2024 Revised: August 29, 2024 Accepted: October 16, 2024 Published online: November 26, 2024 Processing time: 172 Days and 4.3 Hours
Abstract
BACKGROUND
Recent advancements in nanomedicine have highlighted the potential of exosome (Ex)-based therapies, utilizing naturally derived nanoparticles, as a novel approach to targeted cancer treatment.
AIM
To explore the targetability and anticancer effectiveness of small interfering peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 RNA (siPIN1)-loaded soluble a proliferation-inducing ligand (sAPRIL)-targeted Exs (designated as tEx[p]) in the treatment of colon cancer models.
METHODS
tEx was generated by harvesting conditioned media from adipose-derived stem cells that had undergone transformation using pDisplay vectors encoding sAPRIL-binding peptide sequences. Subsequently, tEx[p] were created by incorporating PIN1 siRNA into the tEx using the Exofect kit. The therapeutic efficacy of these Exs was evaluated using both in vitro and in vivo models of colon cancer.
RESULTS
The tEx[p] group exhibited superior anticancer effects in comparison to other groups, including tEx, Ex[p], and Ex, demonstrated by the smallest tumor size, the slowest tumor growth rate, and the lightest weight of the excised tumors observed in the tEx[p] group (P < 0.05). Moreover, analyses of the excised tumor tissues, using western blot analysis and immunohistochemical staining, revealed that tEx[p] treatment resulted in the highest increase in E-cadherin expression and the most significant reduction in the mesenchymal markers Vimentin and Snail (P < 0.05), suggesting a more effective inhibition of epithelial-mesenchymal transition tEx[p], likely due to the enhanced delivery of siPIN1.
CONCLUSION
The use of bioengineered Exs targeting sAPRIL and containing siPIN1 demonstrated superior efficacy in inhibiting tumor growth and epithelial-mesenchymal transition, highlighting their potential as a therapeutic strategy for colon cancer.
Core Tip: This study investigated the potential of bioengineered exosomes (Exs), specifically small interfering peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 RNA-loaded soluble a proliferation-inducing ligand-targeted Exs, in treating colon cancer. By targeting soluble A proliferation-inducing ligand and delivering small interfering peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, these modified Exs demonstrated superior efficacy in inhibiting tumor growth and epithelial-mesenchymal transition compared to standard Ex treatments. The findings highlight the promise of the novel targeted Exs, offering insights into the enhanced targetability and anticancer effectiveness of Ex-based therapies in oncological applications.
