ACS Nano
·
2025
·
IF 16
Xiaotong Chen,Lei Lei,Jiayao Yan,Xingzhou Wang,Lin Li,Qin Liu,Ying Wang,Tianran Chen,Jie Shao,Lixia Yu,Zijian Li,Lijing Zhu,Lifeng Wang,Baorui Liu
Although personalized neoantigen cancer vaccines have emerged as a promising strategy for cancer treatment, challenges remain to develop immune-stimulatory carriers which allow simultaneous transport of adjuvants and vaccines to lymph nodes (LNs). With inherent immunogenicity, genetic plasticity, and efficiency for large-scale production, M13 phages represent an attractive platform for vaccine delivery as natural bionanomaterials. Here, we report the discovery of an anti-CD40 designed ankyrin repeat protein (DARPin) and propose a bifunctional M13 ph age for neoantigen delivery based on this anti-CD40 DARPin protein (M13CD40). M13CD40-based neoantigen vaccines show improved accumulation and prolonged antigen retention in LNs compared with nontargeting phage vaccines due to the abundance of CD40-positive cells in LNs. Besides the intrinsic immunogenicity of phages, M13CD40-based neoantigen vaccines also benefit from additional CD40 stimulation due to multiple copies of anti-CD40 DARPins displayed on M13CD40 phages. Subcutaneous immunization with M13CD40-based neoantigen vaccines results in more robust antigen-specific immune responses and superior antitumor efficacy in poorly immunogenic tumor models compared with nontargeting phage vaccines. Combination therapy with PD-1 blockade further enhances T cell cytotoxicity and improves tumor control. To summarize, our findings highlight M13CD40 as a CD40 nanoagonist as well as an efficient vehicle for LN-targeted delivery of personalized neoantigen 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
ADVANCED MATERIALS
·
2025
·
IF 26.8
Zhixin Zhu,Lulu Jin,Qiaoxuan Wang,Haifei Shi,Ke Cheng,Zhengwei Mao
There is a desperate need for precise nanomedications to treat ischemic cerebral injury. Yet, the drawbacks of poor delivery efficiency and off-target toxicity in pathologic parenchyma for traditional antioxidants against ischemic stroke result in inadequate brain accumulation. M13 bacteriophages are highly phagocytosed by M1-polarized microglia and can be carried toward the neuroinflammatory sites. Here, a bio-active, inhalable, Ce 0.9 Zr 0.1 O 2 -backpacked-M13 phage (abbreviated as CZM) is developed and demonstrates how M13 bacteriophages are taken up by different phenotypes’ microglia. With the M1 microglia's proliferating and migrating, CZM can be extensively and specifically delivered to the site of the ischemic core and penumbra, where the surviving nerve cells need to be shielded from secondary oxidative stress and inflammatory cascade initiated by reactive oxygen species (ROS). With non-invasive administration, CZM effectively alleviates oxidative damage and apoptosis of neurons by eliminating ROS generated by hyperactive M1-polarized microglia. Here, a secure and effective strategy for the targeted therapy of neuroinflammatory maladies is offered by this research.
研究领域:
神经科学
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纳米医学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Liyan Bi,Huangruici Zhang,Wenchao Hu,Jiadong Chen,Yixuan Wu,Hao Chen,Bingqian Li,Zhiyang Zhang,Jaebum Choo,Lingxin Chen
Self-assembled functional nanomaterials with electromagnetic hot spots are crucial and highly desirable in surface-enhanced Raman scattering (SERS). Due to its versatile biological scaffold, the M13 phage has been employed to produce novel nano-building blocks and devices. In this study, we propose a novel M13 phage-based SERS nanocarrier , that utilizes the pVIII capsid in M13 to conjugate Au@Ag core-shell nanorod (Au@AgNR) with linker carboxy-PEG-thiol (M13-Au@AgNR) and the pIII capsid to specifically target Escherichia coli ( E. coli ). The M13-Au@AgNR@DTTC (3,3′- diethylthiocarbocyanine iodide) SERS probe was used to detect E. coli in a concentration range of 6 to 6 × 10 5 cfu/mL, achieving a limit of detection (LOD) of 0.5 cfu/mL. The proposed SERS platform was also tested in real samples, showing good recoveries (92%–114.3%) and a relative standard deviation (RSD) of 1.2%–4.7%. Furthermore, the system demonstrated high antibacterial efficiency against E. coli , approximately 90%, as measured by the standard plate-count method. The investigation provides an effective strategy for in vitro bacteria detection and inactivation.
研究领域:
纳米材料
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2022
·
IF 9.221
Jinxiu Hou,Yi Xu,Shasha Sun,Xiaoli Zhong,Chih-Tsung Yang,Xin Zhou
Label-free SPR is rarely used for biomarker detection in real samples due to its low sensitivity. Herein, we report a phage-based SPR (P-SPR) strategy for the detection of carcinoembryonic antigen (CEA) in undiluted serums. M13 phage is genetically engineered to display an anti-CEA single-chain variable region fragment on pIII protein for antigen targeting and to display the gold binding peptide (GBP) at the pVIII protein for gold nanoparticles (GNPs) binding to form the GNPs decorated M13 phage probe that can amplify the plasmon resonance signal. The proposed P-SPR method demonstrated ultrasensitive detection of CEA within 10 min. Under ideal conditions, P-SPR showed exceptional sensitivity with a limit of detection (LOD) of 0.83 fM, which is approximately 2000 times that of the conventional SPR and four orders of magnitude more sensitive than enzyme-linked immunosorbent assay. In particular, the proposed strategy can cross-validate the SPR results through naked-eye counting of the plaques generated by the P-SPR probes, enabling a reliable dual detection system. In addition, P-SPR scheme has excellent sensing performance for the detection of real samples at concentrations lower than LOD of ELISA. Therefore, the proposed P-SPR strategy holds potential for early detection of tumour biomarkers in liquid biopsy.
研究领域:
生物传感器
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纳米技术
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癌症诊断
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分析化学
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分子生物学
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产品关联
DOI
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 42
·17871-17880
·
IF 7.79
Wenjing Qi,Huimin Yu
Surface immobilization of enzymes on magnetic-recoverable carriers is of great interest and importance for the biocatalysis of relatively large molecules. In this work, the nanosized amino-rich filamentous M13 virus, a versatile biological scaffold, was applied as the unique soft backbone for lipase immobilization. Based on the structure and capsid proteins of M13 phages, the magnetic-recoverable mimic-free-lipases (MFLs) composed of the M13 hydrogels and magnetic particles were developed in two designs. In the first design, nanosized wild M13 phages were crosslinked into a phage hydrogel through the N-terminals of pVIII peptides while NH2-Fe3O4 magnetic nanoparticles (MNPs) were attached to the M13 virus through glutaraldehyde, forming the M13-(NH2-Fe3O4) magnetic phage hydrogel. In the second design, special M13 with Fe3O4 affinity pIII-peptide (FAP-M13) was biopanned for strongly binding towards bare Fe3O4 with the “hook”-like pIII-peptide (N-LPLSTQH-C). TEM observation confirmed the direct grasp of FAP-M13 on bare Fe3O4, forming the magnetic (FAP-M13)-Fe3O4 virus hydrogel. Lipases were uniformly anchored on the phage surface of nanoscale by crosslinking with the N-terminals of pVIII peptides, and then lipase@M13-(NH2-Fe3O4) and lipase@(FAP-M13)-Fe3O4 MFLs were constructed. For both MFLs, high activity recovery yield (>95%) and efficient magnetic separation were characterized. Significantly reduced MNP-usage-amount and enhanced lipase-loading-amount both by about 40 folds were obtained, compared with the conventional NH2-Fe3O4 carriers. The quantified Km and Vmax/Km values were almost equal to those of the free lipases, verifying free-enzyme-mimicking features of the MFLs. High pH-tolerance, wide temperature adaptability, enhanced thermal stability and stable magnetic separation capability of both MFLs were also observed. In particular, the (FAP-M13)-Fe3O4 magnetic virus hydrogel simply using bare Fe3O4 MNPs would be more convenient and economical in the scaled-up biocatalysis.
研究领域:
生物技术
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材料科学
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生物化学
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化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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