Cell Reports Medicine
·
2025
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IF 10.6
Chen Xu,Liting Chen,Guangna Liu,Jiaqi Xu,Wei Lv,Xiaoyu Gao,Peijun Xu,Ming Tang,Yaohe Wang,Xiao Zhao,Guangjun Nie,Keman Cheng,Funan Liu
Oncolytic viruses (OVs) combined with radiotherapy (RT) show promise but are limited by challenges such as poor intravenous delivery and insufficient RT-induced DNA damage. In this study, an oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), is developed to improve delivery, infectivity, immune response, and RT efficacy. The multifunctional polyethylenimine (PEI)-selenium-polyethylene glycol (PEG) (PSSP) enhances intravenous delivery, shields the virus from rapid clearance, and enables targeted delivery to tumor sites after RT. The exposed PEI enhances the infectivity of AD through electrostatic interactions, thereby increasing DNA damage after RT by inhibiting the expression of DNA repair proteins, such as CHEK1 and CDK1. Furthermore, AD-PEI captures and delivers RT-induced tumor-released antigens to lymph nodes, activating robust anti-tumor immune responses. Animal model data demonstrate that RadioOnco overcomes RT resistance, targets distant metastases, and promotes long-term immunity, addressing metastasis and recurrence. In summary, this intravenously injectable OV enhances RT synergy through surface modification with multifunctional materials.
研究领域:
肿瘤学
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病毒学
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辐射生物学
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免疫治疗
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
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IF 15.7
Zhang Jiayu,Yang Jinneng,Luo Jinyan,Wu Weili,Luo Haidan,Wei Wenxia,Lyu Haimei,Wang Yuzhi,Yi Hairong,Zhang Yijing,Fan Zongmin,Lyu Haiwen,Kanakaveti Vishnu Priya,Qin Baifu,Yuan Ping,Yang Runxiang,Zhang Haipeng,Zuo Tao,Felsher Dean W.,Lee Mong-Hong,Li Kai
Oncolytic viruses (OVs) hold promise for cancer treatment. However, the antitumor efficacy is limited. Microbiota plays a pivotal role in cancer treatment and its impact on oncolytic virotherapy is unknown. Here, we show that VSVΔ51 has higher antitumor efficacy for hepatocellular carcinoma in the absence of microbiota in female mouse models. VSVΔ51 infection causes microbiota dysbiosis, increasing most of the gut bacteria abundance, while decreasing the commensal Lactobacillus . VSVΔ51 reduced intestinal expression of SLC20A1 that binds to Lactobacillus acidophilus ( L. acidophilus ) CdpA cell wall protein through IL6-JAK-STAT3 signaling, thereby attenuating attachment and colonization of L. acidophilus . L. acidophilus supplementation confers sensitivity to VSVΔ51 through restoring gut barrier integrity and microbiota homeostasis destroyed by VSVΔ51. In this work, we show that targeting microbiota homostasis holds substantial potential in improving therapeutic outcomes of oncolytic virotherapy.
研究领域:
肿瘤学
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微生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
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IF 18.5
Yuchao Li,Haiyuan Yang,Xiaoqing Zong,Xiaodi Li,Pengfei Yuan,Caiqi Yang,Xinjie Chen,Xiaodie Yan,Yaoqi Wen,Tianci Zhu,Wei Xue,Jian Dai
Nucleic acid drugs are widely used in biomedical fields. However, one of the main challenges in vivo is to selectively deliver nucleic acid drugs to subcellular compartments. To solve this problem, an oncolytic virus-like nanoparticle, OV@FN, is constructed that can directly deliver nucleic acids to the cytoplasm through membrane fusion in response to the slightly acidic environment of the tumor. OV@FN is composed of a nano-core (NA-Zn@G) that can accurately release nucleic acids in response to high concentrations of glutathione in the cytoplasm of tumor cells and a hybrid membrane vesicle (FN) expressing oncolytic virus fusion membrane glycoprotein (mVSV-G). The study findings suggest that OV@FN efficiently and selectively delivers nucleic acids to the cytoplasm of tumor cells, as compared to normal cells. Importantly, FN effectively induces tumor cells to form a syncytium, thus promoting intracellular drug diffusion, and enhancing the gene therapy effect. In vivo gene silencing test shows that OV siR @FN has a significant nucleic acid delivery performance. In the melanoma model, the OV 3pdsR @FN shows remarkable tumor ablation ability and improves the immunosuppressive microenvironment of the tumor site. OV@FN offers a novel approach to designing gene delivery and tumor therapy platforms.
研究领域:
生物医学工程
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肿瘤学
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分子生物学
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产品关联
DOI
高影响因子
International Journal of Oral Science
·
2024
·Vol. 16
·期 1
·1-13
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IF 10.8
Li Shujin,Feng Tian,Liu Yuantong,Yang Qichao,Song An,Wang Shuo,Xie Jun,Zhang Junjie,Yuan Bifeng,Sun Zhijun
N 1 -methyladenosine (m 1 A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m 1 A modification levels. Analysis of m 1 A-associated genes identified TRMT61A as a key m 1 A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m 1 A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m 1 A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m 1 A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m 1 A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
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IF 6.1
Gong Chen,Yuan Yuan,Ying Li,Zushun Xu,Qianyuan He,Zizhen Qin,Han Hu,Congcong Gao,Qi Xu,Qinglei Gao,Fei Li
Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system is the main reason that limits their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses, but it is limited in its uptake efficiency by tumor cells. Herein, we constructed a N- hydroxymethyl acrylamide -b-(N-3- aminopropyl methacrylamide) -b-DMC block copolymers (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also has excellent loading oncolytic virus stability. The data shows that no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibody in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vector can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for modification methods of acrylamide for biomedical applications.
研究领域:
生物医学
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肿瘤学
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病毒学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2022
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IF 18.962
Hanwei Huang,Mengchi Sun,Mingyang Liu,Siwei Pan,Pengfei Liu,Zhenguo Cheng,Jia Li,Huimian Xu,Funan Liu,Zhiqing Pang
Intravenous delivery of oncolytic virus (OVs) is promising in cancer treatment. Unfortunately, fast clearance of OVs and the severe cytokine release syndrome impede its wide application. It has been shown that nanoparticles coated with cell membranes display less toxicity and slower clearance. However, different from conventional nanoparticles, the characteristic spike-like structure and abundant antigens on the surface make it difficult for intravenously delivered OVs to take advantage of cell membrane coating to shield their surface antigens. To overcome this challenge, we, for the first time, used erythrocyte-lipid hybrid membrane vesicle (erythroliposome) to fully encapsulate OVs for their intravenous delivery. We found that adding artificial membranes to cell membranes reduced the fluidity of the membranes, leading to an extraordinary shielding effect on OV antigens. Consequently, circulation of OVs was significantly prolonged and their oncolytic efficacy to metastatic and refractory tumors was markedly enhanced.
研究领域:
肿瘤学
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纳米医学
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生物工程
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免疫学
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DOI
高影响因子
Acta Biomaterialia
·
2024
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IF 9.4
Yi-Shu Li,Lu-Yi Ye,Yan-Xi Luo,Wen-Jie Zheng,Jing-Xing Si,Xue Yang,You-Ni Zhang,Shi-Bing Wang,Hai Zou,Ke-Tao Jin,Tong Ge,Yu Cai,Xiao-Zhou Mou
Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. Statement of significance : Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, Hypoxia effect, and Administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.
研究领域:
肿瘤学
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免疫学
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生物医学工程
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病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Oncolytics
·
2023
·
IF 5.7
Jun Xie,Shaowei Wang,Yunhong Zhong,Ming Gao,Xuezhang Tian,Liting Zhang,Dongli Pan,Qingsong Qin,Bing Wu,Ke Lan,Zhi-Jun Sun,Junjie Zhang
Oncolytic viruses (OVs) encoding various transgenes are being evaluated for cancer immunotherapy. Diverse factors such as cytokines, immune checkpoint inhibitors, tumor-associated antigens, and T cell engagers have been exploited as transgenes. These modifications are primarily aimed to reverse the immunosuppressive tumor microenvironment. By contrast, antiviral restriction factors that inhibit the replication of OVs and result in suboptimal oncolytic activity have received far less attention. Here, we report that guanylate-binding protein 1 (GBP1) is potently induced during HSV-1 infection and restricts HSV-1 replication. Mechanistically, GBP1 remodels cytoskeletal organization to impede nuclear entry of HSV-1 genome. Previous studies have established that IpaH9.8, a bacterial E3 ubiquitin ligase, targets GBPs for proteasomal degradation. We therefore engineered an oncolytic HSV-1 to express IpaH9.8 and found that the modified OV effectively antagonized GBP1, replicated to a higher titer in vitro and showed superior antitumor activity in vivo . Our study features a strategy for improving the replication of OVs via targeting a restriction factor and achieving promising therapeutic efficacy.
研究领域:
肿瘤学
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病毒学
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免疫疗法
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Chemistry
·
2025
·
IF 20.2
Wen Ping,Huang Hanwei,Zhang Ruizhe,Zheng Hanqi,Liang Tingxizi,Zhuang Chuyue,Wu Qing,Wang Junxia,Liu Feng,Zhang Ke,Wu Wei,He Kaixin,Liu Funan,Li Hongjun,Gu Zhen
Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid–liquid phase separation of cholesterol-modified DNA and histones. Unlike a phospholipid-based membrane-bounded vesicle, a coacervate vesicle lacks a membrane structure on the surface and is organized with a high-density liquid layer and a water-filled cavity. Through a straightforward coacervation process, we demonstrate that various biological agents, including virus particles, mRNA, cytokines and peptides, can be innocuously and directly enriched in the liquid phase. In contrast to the droplet-like coacervates that are prone to aggregation challenges, coacervate vesicles display superior kinetic stability, positioning them as a versatile delivery vehicle for biopharmaceuticals. We validate that incorporating oncolytic viruses into these coacervate vesicles endows them with potent oncolytic efficacy and elicits robust anti-tumour immune responses in mouse models.
研究领域:
生物技术
·
药剂学
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癌症研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Signal Transduction and Targeted Therapy
·
2023
·Vol. 8
·期 1
·1-16
·
IF 39.3
Cui Bopei,Song Lifang,Wang Qian,Li Kelei,He Qian,Wu Xing,Gao Fan,Liu Mingchen,An Chaoqiang,Gao Qiushuang,Hu Chaoying,Hao Xiaotian,Dong Fangyu,Zhou Jiuyue,Liu Dong,Song Ziyang,Yan Xujia,Zhang Jialu,Bai Yu,Mao Qunying,Yang Xiaoming,Liang Zhenglun
With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.
研究领域:
肿瘤学
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病毒学
·
分子生物学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
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