Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 15 4 2025 11 15 Hydrogel Micro/Nanostructures for the Delivery of Oncolytic Viruses: Overcoming Limitations and Improving Efficacy 735 749 10.34172/apb.025.45842 EN Chou-Yi Hsu https://orcid.org/0000-0001-7105-1161 Saade Abdalkareem Jasim https://orcid.org/0009-0009-0821-5843 Jasur Alimdjanovich Rizaev Tina Saeed Basunduwah https://orcid.org/0009-0000-7386-051X Vikrant Abbot Mamata Chahar Mohammed Asiri Abbas Fadhel Ali Alexey Yumashev https://orcid.org/0000-0002-5184-0195 Ahmed Hussein Zwamel REVIEW 10.34172/apb.025.45842 2025 05 22 2025 09 25 Oncolytic viruses (OVs) have attracted accumulating attention in cancer therapy owing to their ability to replicate in and kill tumor cells, resulting in the stimulation of immune responses for eradicating residual and distant malignant cells. Despite milestone achievements in the development of OVs, which led to the U.S. Food and Drug Administration (FDA) approval of talimogene laherparepvec (T-VEC) in 2015 against melanoma, there are some hurdles limiting their translation from the bench to the clinic, such as non-specific localization, host immune response against OVs and their clearance, and low efficiency as a monotherapy. Delivery of OVs with nano-biomaterials is a promising approach to address the drawback of oncolytic virotherapy. Hydrogels, with their tunable characteristics and versatile properties, offer a promising platform for the controlled release, precise delivery, and therapeutic enhancement of OVs in combination with other therapeutic agents in the treatment of cancers. This review aims to provide a deep insight into the types and development of OVs and their application in clinical trials and then will discuss the characteristics of hydrogels and how they improve the therapeutic efficacy of OVs.