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REVIEW ARTICLE

Complementing a pair of distinct engineered oncolytic viruses with functionalized magneto-nanoparticles for enhanced cancer targeting therapy: A revisit

Stephene S. Meena1,2* ,  Geofrey F. Soko1,2 ,  Alita Mrema1 ,  Jerry Ndumbalo1 ,  Harrison R. Chuwa3 ,  Caroline R. Sway1 ,  Emmanuel Lugina1 ,  Julius Mwaiselage1 ,  Ramadhani Chambuso4*
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1 Department of Clinical Oncology, Directorate of Medical Services, Ocean Road Cancer Institute, Dar es Salaam, United Republic of Tanzania
2 Jiangzhong Cancer Research Center, Jiangxi Engineering Research Center for Translational Cancer Technology, Jiangxi University of Chinese Medicine, Nanchang, Jiangxi Province, China
3 Department of Oncology, Faculty of Internal Medicine, Aga Khan University & Aga Khan Health Service, Dar es Salaam, United Republic of Tanzania
4 Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America
Tumor Discovery, 025190038 https://doi.org/10.36922/TD025190038
Received: 9 May 2025 | Revised: 17 August 2025 | Accepted: 20 August 2025 | Published online: 5 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Oncolytic viruses (OVs) are emerging as promising cancer immunotherapeutic agents due to their cancer-directed oncolysis and ability to induce potent and durable anticancer immune responses. They have shown encouraging results even in tumors that are resistant to conventional therapies. However, the therapeutic efficacy of OVs is hindered by antiviral immune responses that eliminate OVs before they reach their target site and the tumor stroma, limiting intratumoral virus spread in the tumor microenvironment (TME). To address these challenges, various strategies have been developed to shield OVs from immunosurveillance by loading viruses onto/into cellular carriers, extracellular vesicles, liposomes, and nanoparticles. Despite notable improvements in viral shielding and targeting strategies, inefficient intratumoral viral penetration remains a critical obstacle. In the TME, the tumor stroma accounts for 90% of the entire tumor mass, comprising non-cancerous cells and extracellular matrix. Since OVs are engineered to target only cancer cells, their cytolytic efficacy is counteracted by the tumor stroma. Therefore, innovative approaches are necessary to enhance the penetration of viruses within tumors, thereby increasing the efficacy of oncolytic virotherapy. This review aims to provide a comprehensive overview of OVs in terms of clinical applications, successes, and limitations, while also discussing future directions for enhancing the targeted delivery and intratumoral penetration of OVs.

Keywords
Virotherapy
Oncolytic viruses
Tumor microenvironment
Cancer immunotherapy
Targeted cancer therapy
Functionalized magneto-nanoparticles
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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