ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
This article is part of the Research TopicNanomedicine in Cancer Therapy: Advances and ChallengesView all 4 articles
Extracellular Vesicles Delivering TIMP-2 Modulate MMP-1, MMP-2, and MMP-9 Expression in Human Lung Adenocarcinoma A549 cells
Provisionally accepted
Agnieszka Stawarska1
Magdalena Bamburowicz-Klimkowska1*
Maciej Małecki1Anna M. Nowicka2Żaneta Słyk1
Agata Kowalczyk2Alicja Targonska3Ireneusz P. Grudzinski1*- 1Medical University of Warsaw, Warsaw, Poland
- 2Uniwersytet Warszawski, Warsaw, Poland
- 3Instytut Biologii Doswiadczalnej im Marcelego Nenckiego Polskiej Akademii Nauk, Warsaw, Poland
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ABSTRACT Background/Objectives: Extracellular vesicles (EVs) carrying therapeutic cargos represent a promising strategy for cancer treatment by enabling the targeted delivery of genetic material directly to cancer cells. This study aimed to evaluate the effect of EVs loaded with the TIMP-2 gene on the expression of matrix metalloproteinases (MMPs 1, 2, and 9) in lung cancer cells (A549). Methods: EVs derived from A549 cells were isolated by gradient centrifugation and ultracentrifugation. The coding sequence for TIMP-2 (tissue inhibitor of metalloproteinases 2) was amplified by PCR using cDNA derived from HUVEC cells. As-constructed plasmid (pTIMP-2) was introduced into the EVs by electroporation, and then the pTIMP-2-implanted EVs were subjected to PCR and NTA analysis. Additionally, the activity of MMP-1, MMP-2, and MMP-9 was determined by voltammetry in intact A549 cells and in A549 culture media. Results: Electroporation was found to demonstrate a good potential as an exogenous technique for uploading plasmid DNA into EVs. The results demonstrated that the as-uploaded EVs carrying the pTIMP-2 gene cargo do not broadly alter the overall balance of MMP-1 in pristine A549 cells. However, pTIMP-2-loaded EVs significantly modulate MMP-2 and MMP-9 expression in these cells, highlighting their potential as biological therapeutic moieties. Conclusions: Our findings suggest a rational approach for exploring EV-based gene transfer targeting MMPs in lung cancer.
Keywords: Electroporation, extracellular vesicles, gene encapsulation, Lung cancer cells, Matrix Metalloproteinases, Tissue inhibitor of metalloproteinase
Received: 09 Jan 2026; Accepted: 13 Feb 2026.
Copyright: © 2026 Stawarska, Bamburowicz-Klimkowska, Małecki, Nowicka, Słyk, Kowalczyk, Targonska and Grudzinski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Magdalena Bamburowicz-Klimkowska
Ireneusz P. Grudzinski
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