Materials Today Bio
·
2025
·
IF 10.2
Ruirong Wu,Xiufeng Wu,Lan Zhang,Feng Zhang,Yang Ding,Yong Mao,Jiang Ni
Viral vectors share unparalleled gene-transfection efficiency due to protein capsid-mediated target-cell recognition and efficient cellular translocation, but clinical applications are seriously hampered by potential biosafety issues. Herein, we develop a virus-mimicking nanoparticle to enable safe, selective, and efficient TRAIL-expressing plasmid (pTRAIL) transfection for site-specific apoptosis and bystander effects. For preparation, a reactive oxygen species (ROS)-responsive phenylboronic acid-rich quaternized polymer (CRP) is synthesized for electrostatic compression of pTRAIL and coordinative coupling for apolipoprotein A-I with iRGD peptide conjugation, which is termed as iaCRP/pTRAIL nanoparticles with “gene core-protein shell” structure. The tailored virus-mimicking nanoparticles could prevent pTRAIL payloads from serum elimination, accompanied by site-specific accumulation and penetration. After cellular internalization, ROS-triggered nanoparticles disassembly could further perform burst pTRAIL release and high TRAIL expression. Our findings confirm TRAIL-derived apoptosis and bystander effects, giving in vivo tumor inhibition of ∼80 % and metastasis suppression of over 90 %. Collectively, the virus-mimicking strategy provides novel insights into bionic gene delivery and transfection design for efficient and safe oncotherapy.
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
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2025
·
IF 5.6
Hong-Li Wang,ChuanMing Yu,Qiangling Yin,Jin-Wei Bu,Shuang Feng,Di Ning,Shu-Lin Liu,Linlin Liu,Zhi-Gang Wang
Drug therapy is an important measure to reduce the morbidity and mortality of influenza. However, small molecule drugs have inherent limitations, such as poor water solubility, non-specific biological distribution, and susceptibility to degradation during blood circulation, which impose a great burden on patients, both physically and mentally. Inspired by the high levels of reactive oxygen species (ROS) at the site of influenza A virus (IAV) infection, we have developed an intelligent responsive virus-mimicking nanodrug (Zana@HA-Lip) based on a biomimetic approach, reduces the damage of the drug to normal tissues or organs while achieving the purpose of antiviral therapy by precisely releasing the drug at the lesion site. Zana@HA-Lip offers distinct advantages regarding lesion site tropism, duration of action, and efficiency of release in response to ROS. This work not only presents a safe and effective strategy for alleviating lung injury caused by IAV infection but also introduces a new concept for the precise customization of virus-mimicking nanocarriers.
研究领域:
药剂学
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纳米技术
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病毒学
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生物医学工程
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靶向治疗
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ya Chu,Luyao Wang,Xi Huang,Cenxi Lao,Lin Luo,Jingyi Chen,Fangfei Jin,Lili Zhao,Kaiyuan Hu,Miao Lv,Xianjing Li,Yong Yang,Weijun Zhao,Wenguang Wang
The major challenge for in-situ cancer vaccines is to activate the DCs within the immunosuppressive tumor to initiate tumor-specific immune responses. By contrast, oncolytic viruses can always activate intratumoral DCs to initiate virus-specific immunity to eliminate viruses which will in turn reduce the anti-tumor effect of these viruses. To bridge the two approaches, we developed virus-mimicking nanoparticles (V-mimics) through self-assembly of artificial cyclic gadolinium-based GAMP (c·Gd·GAMP, a STING agonist), double-stranded RNA analog (Poly I: C), and indocyanine green (ICG). Within the V-mimics, c·Gd·GAMP and Poly I: C can simulate the DNA and RNA produced by virus replication to reverse the inhibition of the immunosuppressive tumor microenvironment on DCs by promoting the IFN-β secreting via activating nucleic acid sensors, thereby eliciting anti-tumor immune response in a manner akin to the immune response triggered by viruses. Notably, the V-mimics significantly promoted IFN-β secretion, enhanced DC maturation, and elicited robust tumor-specific immune memory when combined with photothermal therapy. In multiple tumor models, significant tumor inhibition was observed, including a metastasis and recurrence model. Therefore, leveraging the virus-mimicking particles to simulate the mechanism of virus-initiated specific immune responses to activate the intratumoral dendritic cells may open up new strategies for in-situ cancer vaccines.
研究领域:
肿瘤学
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免疫学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yi Zhang,Mengting Xiong,Xiaomin Ni,Jingrou Wang,Hehui Rong,Yuqing Su,Shihui Yu,Imran Shair Mohammad,Sharon Shui Yee Leung,Haiyan Hu
Protein and peptide drugs orally suffer from extremely low bioavailability principally for the complicated gastrointestinal environment along with the difficulty of passing through the mucus layer and the underlying epithelium. In our work, we fabricated mesoporous silica nanoparticles with modification groups (MSN-NH2@COOH/CPP5) that effectively penetrated the mucus layer and passed through the intestinal epithelium by mimicking the virus surface. Naked nanoparticles were prepared with inner pores of 6 nm diameter to allow efficient insulin loading and coated with the cationic cell-penetrating KLPVM peptide and the anionic glutaric anhydride to yield hydrophilic MSN-NH2@COOH/CPP5 with a ζ-potential of −0.49 mV. The apparent permeability coefficient of virus-mimicking nanoparticles was 14.61 × 10–5 cm/s. The virus-mimicking nanoparticles showed dramatically lower binding to mucin and faster penetration of the mucus layer than positively charged nanoparticles (MSN@NH2) with a ζ-potential of +35.00 mV. The KLPVM peptide enhanced the uptake of MSN-NH2@COOH/CPP5 by coculturing Caco-2 and E12 cells as an intestinal epithelium model. MSN-NH2@COOH/CPP5 enhanced apical-to-basal transcytosis for being internalized primarily through caveolae-mediated endocytosis. Indeed, for MSN-NH2@COOH/CPP5, the transepithelial transport of the Caco-2 cell monolayer was 2.4-fold higher than MSN@NH2 and 2.0-fold higher than MSN-NH2@COOH. In vitro, loading insulin into nanoparticles maintained the bioactivity of the protein under simulated intestinal conditions. Insulin loaded into MSN-NH2@COOH/CPP5 reduced the diabetic rats’ blood glucose level by nearly 50%. The bioavailability of insulin encapsulated in the MSN-NH2@COOH/CPP5 nanoparticles was 2.1-fold more than insulin when administered directly into the jejunum. Nanoparticles with modifications indicated no significant toxicity in in vitro or in vivo preliminary studies. The obstacles of the mucus layer and intestinal epithelium may be effectively conquered by these virus-mimicking nanoparticles for oral delivery of protein and peptide drugs.
研究领域:
药学
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纳米技术
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Wenyuan Liu,Bo Hou,Dewei Ma,Mingwei Peng,Hongli Mao,Wei Liu,Zhongwei Gu,Siyuan Chen
Transdermal delivery is an attractive route for the treatment of skin disease. However, its therapeutic effectiveness is significantly hampered by the stratum corneum and cell membrane barriers. Herein, we reported a novel liposomes incorporated microneedles (MNs) delivery platform to address these two key challenges. Conventional liposomes were surface modified with membrane-anchoring fusogenic proteins mimicking pH-responsive, comb-like pseudopeptides containing relatively long alkyl side chains. The liposomes-containing MNs were fabricated with biodegradable and biocompatible silk fibroin with sufficient mechanical strength using micromolding technology. The degradation and release profile of liposomes from the MNs delivery platform can be manipulated by controlling the liposomes to silk fibroin ratio, and the released liposomes well-maintained their original spherical shape and pH-responsive functionality. Remarkably enhanced in vitro skin permeation was observed in the polymer modified liposomes incorporating MNs delivery platform compared to the ones without MNs facilitation. Enhanced cellular uptake and potency against cancer cells of the pH-responsive, comb-like pseudopeptides modified liposomes incorporating MNs delivery platform were demonstrated. These results suggest its potential applications for efficient skin penetration and enhanced cellular uptake, which is of crucial importance for skin disease treatment.
研究领域:
药剂学
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生物医学工程
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药物递送系统
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纳米技术
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皮肤科学
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2022
·Vol. 34
·期 37
·2204585
·
IF 32.086
Xiu Zhao,Yiyang Wang,Wenxiao Jiang,Qiongwei Wang,Jun Li,Zhiyang Wen,Airong Li,Kaixiang Zhang,Zhenzhong Zhang,Jinjin Shi,Junjie Liu
Virus-based immunotherapy is a promising approach to treat tumor. Closely mimicking the structure and sequential infection processes of natural viruses is highly desirable for effective tumor immunotherapy but remains challenging. Here, inspired by the robust innate immunity induced by herpesvirus, a herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) is engineered for tumor therapy by mimicking the structure and infection processes of herpesvirus. In this biomimetic system, DNAzyme-loaded manganese‑doped zeolitic imidazolate framework‑90 (ZIF-90) nanoparticles (ZM@TD) mimic the virus nucleocapsid containing the genome; the erythrocyte membrane mimics the viral envelope; and two functional peptides, RGD and HA2 peptides, resemble the surface glycoprotein spikes of herpesvirus. Vir-ZM@TD can both effectively evade rapid clearance in the blood circulation and closely mimic the serial infection processes of herpesvirus, including specific tumor targeting, membrane fusion-mediated endosomal escape, and TFAM (transcription factor A, mitochondrial) deficiency-triggered mitochondrial DNA stress, as well as the release of manganese ions (Mn 2+ ) from organelles into the cytosol, ultimately effectively priming cGAS-STING pathway-mediated innate immunity with 68% complete regression of primary tumors and extending by 32 days the median survival time of 4T1-tumor-bearing mice.
研究领域:
生物医学工程
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癌症免疫疗法
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纳米技术
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分子生物学
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细胞生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2021
·Vol. 8
·期 13
·2004670
·
IF 16.806
Zheying Meng,Yang Zhang,E Shen,Wei Li,Yanjie Wang,Krishnan Sathiyamoorthy,Wei Gao,Michael C. Kolios,Wenkun Bai,Bing Hu,Wenxing Wang,Yuanyi Zheng
The low delivery efficiency of nanoparticles to solid tumors greatly reduces the therapeutic efficacy and safety which is closely related to low permeability and poor distribution at tumor sites. In this work, an “intrinsic plus extrinsic superiority” administration strategy is proposed to dramatically enhance the mean delivery efficiency of nanoparticles in prostate cancer to 6.84% of injected dose, compared to 1.42% as the maximum in prostate cancer in the previously reported study. Specifically, the intrinsic superiority refers to the virus-mimic surface topology of the nanoparticles for enhanced nano–bio interactions. Meanwhile, the extrinsic stimuli of microbubble-assisted low-frequency ultrasound is to enhance permeability of biological barriers and improve intratumor distribution. The enhanced intratumor enrichment can be verified by photoacoustic resonance imaging, fluorescence imaging, and magnetic resonance imaging in this multifunctional nanoplatform, which also facilitates excellent anticancer effect of photothermal treatment, photodynamic treatment, and sonodynamic treatment via combined laser and ultrasound irradiation. This study confirms the significant advance in nanoparticle accumulation in multiple tumor models, which provides an innovative delivery paradigm to improve intratumor accumulation of nanotherapeutics.
研究领域:
纳米技术
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癌症研究
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生物医学工程
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诊疗学
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产品关联
DOI
PubMed
高影响因子
GIANT
·
2020
·
IF 0
Wenbo Zhang,Zihe Zhai,Shenyu Huang,Zhengwei Mao,Yixian Zhang,Changyou Gao
The delivery of nanomaterials or therapeutics into cells takes a decisive role for their applications in nanomedicine. Nature's creations such as viruses provide valued inspiration for design of nano-architectures in cellular delivery. We report herein the fabrication of biodegradable and biocompatible nanoparticles (NPs) with viral-mimicking morphology and constituents as a nanoplatform, which has rarely been reported to the best of our knowledge, for promoting cellular uptake and achieving high therapeutic efficiency in vivo . The chitosan-porphyrin-based NPs were endowed with a viral-imitating morphology through a novel pH-responsive decomposition-induced self-assembly method. By successive conjugation of Tat peptides and modification of lipids, morphological and constituent viral-mimicking NPs were obtained. Compared with the counterpart of non-viral-mimicking NPs, the viral-mimicking NPs showed prominent superiority in enhancing cell internalization (10 times higher). Loading of near-infrared photosensitizer– indocyanine green into these NPs demonstrated the striking capability of the viral-mimicking nanoparticles in therapeautic delivery and photothermal anti-tumor effect in vitro and in vivo . This concept and strategy provides an enlightening methodology on the design and fabrication of therapeutic delivery systems, which is significant for nanobiotechnology.
研究领域:
纳米医学
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癌症治疗
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生物材料
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
危险品化学品经营许可证（带存储）