Jinliang Xu , Xiaoxiao Liu , Junqiang Ding , Hanchang Zhang , Tingting Yao , Sha Li , Rong Yang , Nianhui Yu , Qi Yue , Changyou Zhan , Xihui Gao
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引用次数: 0
Abstract
Oncolytic adenoviruses (OA) are promising therapeutics for glioblastoma (GBM) due to their unique capability of selectively lysing tumor cells and activating the immune response. However, their therapeutic potential is often impeded by limited cellular internalization caused by low expression of OA receptors, as well as restricted OA proliferation due to antiviral responses. In this work, a novel type of OA, named nanosynergist-engineered OA (nsOA), was developed by functionalizing the viral surface with siRNA-loaded hyperbranched polymers. The nanosynergist not only enhanced the infectivity of OA but also augmented virus replication, ultimately potentiating their oncolysis efficacy. We revealed that the enhanced replication of the virus was initiated by the downregulation of signal transducer and activator of transcription-3, which suppressed the transcription of interferon-stimulated genes, ultimately circumventing the antiviral defense of tumor cells. Furthermore, the innate ability of OA to disrupt endosomal membranes was found to improve the endosomal escape of the nanosynergist, creating synergistic effect that amplified the therapeutic benefits. A single dose of nsOA markedly increased the production of progeny viruses and prolonged the survival of mice. Collectively, these results provide an effective and valuable strategy to engineer OA, which may lead to innovative immunotherapies for various cancers.
期刊介绍:
Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.