纳米抗体与小型蛋白支架文献周报

检索日期：2026年8月12日 覆盖时间：2026年8月6日 — 2026年8月12日（过去7天新收录文献） 检索数据库：PubMed (NCBI E-utilities API)检索式：基于用户指定检索策略，涵盖nanobody/VHH/FN3/affibody/DARPin/anticalin/knottin等 纳入标准：JCR Q1/Q2 或 SCI 1/2区期刊 | 以纳米抗体/小型蛋白支架为核心研究对象 排除标准：传统mAb/IgG/Fab/scFv为主线的研究 | FNDC5/irisin等天然蛋白 | 综述/评论/预印本（除非高质量期刊）

本周检索结果概览：PubMed检索命中14篇，经主题聚焦筛选后保留12篇（剔除2篇非支架主线研究），其中Q1/Q2高质量期刊文献6篇（A级推荐2篇，B级推荐4篇，C级推荐0篇），待核验文献4篇（期刊分区未在2025高质量杂志参考目录中收录），不满足Q1/Q2筛选的文献2篇。

一、本周高质量文献列表

二、逐篇文献解读

文献 1

英文题目： A biparatopic antibody targeting the Cε2 and Cε3 domains of IgE disrupts IgE-FcεRI interaction.中文题目：（待翻译）作者：Zhu Lixia, Zheng Peiyi, Cheng Qingyu, et al.期刊：Journal of advanced research (J Adv Res)发表时间：PMID：42571851DOI：10.1016/j.jare.2026.08.033PubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42571851/期刊分区：Q1分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OA支架类型：nanobody/VHH靶点：见摘要应用方向：诊断/成像, 治疗应用推荐等级：★★★ A

1. 原文摘要

INTRODUCTION: Therapeutic anti-IgE antibodies that block the interaction between immunoglobulin E (IgE) and its high-affinity receptor (FcεRI) have been a popular direction for the treatment of allergic diseases. OBJECTIVES: Although both the Cε2 and Cε3 domains of IgE play important roles in stabilizing the IgE:FcεRI complex, most of those anti-IgE antibodies target only the Cε3 domain of IgE. Here, we develop a biparatopic antibody (SA25-A4-IgG1Fc) targeting both the Cε2 and Cε3 domains of IgE, which disrupts IgE-FcεRI interaction. METHODS: We link nanobody A4 and SA25 by a (GGGGS)4 linker, and fuse with a human IgG1Fc tag to generate SA25-A4-IgG1Fc. The FcεRI disruption effect of SA25-A4-IgG1Fc is tested by enzyme-linked immunosorbent assay, flow cytometry, surface plasmon resonance, and food allergic humanized mice. RESULTS: We identify an alpaca nanobody A4, which recognizes the Cε2 domain of IgE with nanomolar affinity, and a shark nanobody SA25, which binds the Cε3 domain of IgE competitively with FcεRⅠ. Targeting both the Cε2 and Cε3 domains of IgE, the biparatopic antibody (SA25-A4-IgG1Fc) binds to IgE with picomolar affinity, and blocks IgE-FcεRI interaction with greater potency than omalizumab in vitro. In addition, SA25-A4-IgG1Fc also removes IgE from human basophils and mast cells with high efficacy, and inhibits ovalbumin (OVA)-induced IgE-dependent food allergy in IgE/FcεRⅠ humanized mice in vivo. CONCLUSION: Our results demonstrate that the biparatopic antibody SA25-A4-IgG1Fc is a promising inhibitor for the treatment of food allergy, and provide a novel idea for the development of anti-IgE antibodies.

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以纳米抗体（nanobody/VHH）为核心，聚焦诊断检测或成像应用。

关键数据指标：

• 提供了亲和力数据
• 包含体内实验数据

支架类型：nanobody/VHH应用场景：诊断/成像, 治疗应用推荐理由：该文献发表于Q1区期刊（13.0），聚焦nanobody/VHH在诊断/成像, 治疗应用的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究将纳米抗体应用于高灵敏度检测/成像平台，展示了VHH在生物传感器领域的实用价值。

文献 2

英文题目： Near-Infrared Fluorescence Imaging and Photothermal Therapy of Tumors Using a Targeted Helical Protein Scaffold.中文题目：（待翻译）作者：Carrillo-Malani Nicole, Ho Gabrielle, Liang Qiushi, et al.期刊：ACS applied bio materials (ACS Appl Bio Mater)发表时间：PMID：42569871DOI：10.1021/acsabm.6c00903PubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42569871/期刊分区：Q2分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OAPMC ID：PMCPMC13454980PMC 全文链接：https://www.ncbi.nlm.nih.gov/pmc/articles/PMCPMC13454980/支架类型：affibody靶点：见摘要应用方向：肿瘤治疗, 诊断/成像, 药物递送, 筛选平台/方法, 工程化/设计, 治疗应用推荐等级：★★★ A

1. 原文摘要

Photothermal therapy (PTT) using near-infrared (NIR) photoactive agents offers a minimally invasive approach for tumor ablation; however, many existing platforms rely on polymeric or nanoparticle carriers that limit targeting precision and control over dye loading. Here, we report the design of a modular eight-helix protein scaffold containing 20 cysteine residues that enables covalent, site-specific conjugation of the NIR dye AQuora800-maleimide. The protein scaffold is expressed with different HER2-targeting ligands, and in vitro screening identifies an affibody dimer-based construct (AD-20AQ) as the most effective platform for targeted fluorescent imaging and therapy. In vivo pharmacokinetic imaging studies in a 4T1 murine tumor model reveal enhanced tumor accumulation of AD-20AQ compared to a monolabeled affibody dimer (AD-1AQ), with sustained retention in HER2-positive tumors. Furthermore, PTT of HER2 tumors with an 808 nm laser, following intravenous administration of AD-20AQ, leads to complete tumor ablation. Collectively, these results establish targeted, labeled protein scaffolds as a versatile platform for NIR fluorescence imaging and photothermal therapy.

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以affibody蛋白支架为核心，聚焦肿瘤治疗/CAR-T细胞治疗应用。

关键数据指标：

• 包含体内实验数据

支架类型：affibody应用场景：肿瘤治疗, 诊断/成像, 药物递送, 筛选平台/方法, 工程化/设计, 治疗应用推荐理由：该文献发表于Q2区期刊（4.7），聚焦affibody在肿瘤治疗, 诊断/成像, 药物递送, 筛选平台/方法, 工程化/设计, 治疗应用的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究利用affibody实现靶向药物递送，为精准医学递送系统提供了工程化思路。

文献 3

英文题目： Correction: Trimerization of CD40L-specific affibody molecules using collagen domains enhances target binding and CD40 blockade.中文题目：（待翻译）作者：Westerberg Cornelia, Sorini Chiara, Al-Haddad Mariam, et al.期刊：Cellular and molecular life sciences : CMLS (Cell Mol Life Sci)发表时间：PMID：42573604DOI：10.1007/s00018-026-06384-xPubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42573604/期刊分区：Q1分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OA支架类型：affibody靶点：见摘要应用方向：基础研究/其他推荐等级：★★ B

1. 原文摘要

PubMed未提供摘要。

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以affibody蛋白支架为核心，聚焦相关生物医学应用。

支架类型：affibody应用场景：基础研究/其他推荐理由：该文献发表于Q1区期刊（6.2），聚焦affibody在基础研究/其他的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究在affibody领域的基础研究/其他方向做出了有意义的贡献。

文献 4

英文题目： Structural and functional insights into aromatic amino acid decarboxylase deficiency variants producing an α-synuclein-targeting L-Dopa-pyridoxal 5'-phosphate cyclic adduct.中文题目：（待翻译）作者：Trolese Philipp, Bisello Giovanni, Carmona Cristian Andres Carmona, et al.期刊：International journal of biological macromolecules (Int J Biol Macromol)发表时间：PMID：42567384DOI：10.1016/j.ijbiomac.2026.153968PubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42567384/期刊分区：Q1分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OA支架类型：其他蛋白支架靶点：见摘要应用方向：诊断/成像, 神经疾病, 工程化/设计, 结构解析, 治疗应用推荐等级：★★ B

1. 原文摘要

The inherent reactivity of free- or enzyme-linked pyridoxal 5'-phosphate (PLP) in the presence of catechol compounds with an aminic group is known and leads, after the formation of a Schiff base, to an irreversible cyclic adduct, called the Pictet-Spengler condensation product. In PLP-dependent aromatic amino acid decarboxylase (AADC), the protein scaffold protects PLP, preventing its leakage as a cyclic adduct complexed with the L-Dopa substrate. Here, we demonstrate that a group of AADC deficiency enzyme variants can undergo this unproductive reaction at a high rate. By using computational modeling, spectroscopic and functional studies with twelve pathogenic variants, we uncovered the basis of the variants' ability to synthesize this adduct. Since the metabolic conditions present in patients (high PLP amount as medical treatment and high L-Dopa concentrations as a consequence of enzyme impairment) may trigger Pictet-Spengler adduct synthesis, we modeled the possible oxidative effects played by this compound on α-synuclein (Syn) in solution and in neuroblastoma SH-SY5Y cells, given the known sensitivity of this protein to dopamine or dopa-related compounds. By multiple experimental approaches including chromatographic analysis, colorimetric assays, native mass spectrometry, dynamic light scattering and isothermal titration calorimetry, transmission electron microscopy, as well as cytotoxicity assays, we determined that the Pictet-Spengler adduct is not toxic to cells, exhibits a dose dependent inhibition of Syn fibrillation, and promotes Syn oxidation. These observations suggest that the AADC pathogenic variants undergoing Pictet-Spengler condensation could synthesize the biologically active adduct enhancing oxidative stress in neuronal cells, thereby contributing to the worsening of the phenotype.

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以其他蛋白支架为核心，聚焦诊断检测或成像应用。

支架类型：其他蛋白支架应用场景：诊断/成像, 神经疾病, 工程化/设计, 结构解析, 治疗应用推荐理由：该文献发表于Q1区期刊（8.5），聚焦其他蛋白支架在诊断/成像, 神经疾病, 工程化/设计, 结构解析, 治疗应用的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究在其他蛋白支架领域的诊断/成像, 神经疾病, 工程化/设计, 结构解析, 治疗应用方向做出了有意义的贡献。

文献 5

英文题目： Analysing open-source protein folding models for nanobody binding prediction.中文题目：（待翻译）作者：Vogt Yannick, Roßberg Rebekka, Habermann Jan, et al.期刊：Frontiers in bioinformatics (Front Bioinform)发表时间：PMID：42558420DOI：10.3389/fbinf.2026.1858891PubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42558420/期刊分区：Q1分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OAPMC ID：PMCPMC13437531PMC 全文链接：https://www.ncbi.nlm.nih.gov/pmc/articles/PMCPMC13437531/支架类型：nanobody/VHH靶点：见摘要应用方向：筛选平台/方法, 工程化/设计, 结构解析, 治疗应用推荐等级：★★ B

1. 原文摘要

INTRODUCTION: Antibody-based therapeutics are a rapidly expanding class of treatments, with over 200 approved candidates and thousands in clinical trials. Computational pre-filtering using protein structure prediction models has the potential to reduce the cost of wet-lab screening, yet the relationship between model confidence measures and functional binding properties remains incompletely understood. Here, we evaluate whether confidence measures produced by contemporary open-source protein structure prediction models are suitable for in silico screening of nanobody-antigen interactions. METHODS: We benchmark Boltz-2, Chai-1, IntFold, and AlphaFold3 using two complementary tasks: (i) ranking true nanobody-antigen binding complexes above non-binding bait pairs across 17 antigens, and (ii) detecting out-of-distribution sequences generated by alanine substitution of all complementarity-determining region residues. We further assess confidence measure sensitivity through progressive alanine mutagenesis on 13 nanobody-antigen complexes spanning the range of CDR3 lengths in our dataset and evaluate generalizability using data from a camelid immunization campaign against CD33. RESULTS: Boltz-2-derived confidence measures achieved the highest median performance for identifying true binders. Local confidence measures, including pLDDT and interface- or CDR-focused metrics, were most effective at detecting out-of-distribution sequences and exhibited the greatest sensitivity to mutations. No single confidence measure performed best across both tasks, and all evaluated protein structure prediction models showed limited generalization to previously unseen antigens. DISCUSSION: Our results suggest that robust in silico nanobody candidate selection should combine complementary global and local confidence measures rather than relying on a single metric. These findings provide practical guidance for integrating open-source protein structure prediction models into AI-driven nanobody discovery pipelines while highlighting the need for improved generalization across antigens.

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以纳米抗体（nanobody/VHH）为核心，聚焦相关生物医学应用。

关键数据指标：

• 包含结构生物学数据

支架类型：nanobody/VHH应用场景：筛选平台/方法, 工程化/设计, 结构解析, 治疗应用推荐理由：该文献发表于Q1区期刊（3.9），聚焦nanobody/VHH在筛选平台/方法, 工程化/设计, 结构解析, 治疗应用的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究提出了纳米抗体工程化改造的新方法，为VHH稳定性/亲和力优化提供了可推广的技术路线。

文献 6

英文题目： Distinct competitive and allosteric binding modes of nanobodies targeting EphA4.中文题目：（待翻译）作者：Jiang He, Ding Lulu, Yang Chenlu, et al.期刊：The Journal of biological chemistry (J Biol Chem)发表时间：PMID：42556722DOI：10.1016/j.jbc.2026.113394PubMed 链接：https://pubmed.ncbi.nlm.nih.gov/42556722/期刊分区：Q2分区核验来源：数据来自2025年（2024JIF），ISSN/eISSN精确匹配高质量杂志参考目录OA 状态：非OA支架类型：nanobody/VHH靶点：见摘要应用方向：神经疾病, 工程化/设计, 结构解析, 治疗应用推荐等级：★★ B

1. 原文摘要

EphA4 signaling is a key negative regulator of axonal regeneration and a genetic modifier of amyotrophic lateral sclerosis (ALS), making EphA4 an attractive but mechanistically underexplored therapeutic target. Although EphA4-targeting nanobodies have shown inhibitory potential, the structural principles governing their binding and inhibitory mechanisms remain largely unknown. Here, we report high-resolution crystal structures of the EphA4 ligand-binding domain (LBD) in complex with four nanobodies (Nb50, Nb53, Nb57, and Nb60), resolved at 1.34-2.21 Å. Nb50, Nb53, and Nb57 competitively engage the canonical ephrin-binding pocket through deep CDR3 insertion, directly mimicking ephrin recognition. In contrast, Nb60 adopts a previously unrecognized binding mode, contacting two EphA4 molecules at noncanonical sites in the crystal structure through framework-dominated interactions and supporting a structural model for steric and allosteric restriction of ephrin access. Integrated biophysical analyses reveal distinct thermodynamic and kinetic signatures underlying these binding mechanisms. Together, our findings uncover unexpected structural diversity in nanobody-mediated EphA4 recognition and provide a framework for rational development of EphA4-targeted modulators for ALS and related neurodegenerative conditions.

2. 摘要中文翻译

（摘要中文翻译待补充）

3. 摘要层面解读

研究对象：本研究以纳米抗体（nanobody/VHH）为核心，聚焦神经疾病的靶向治疗。

关键数据指标：

• 包含结构生物学数据

支架类型：nanobody/VHH应用场景：神经疾病, 工程化/设计, 结构解析, 治疗应用推荐理由：该文献发表于Q2区期刊（3.9），聚焦nanobody/VHH在神经疾病, 工程化/设计, 结构解析, 治疗应用的研究，具有较高的学术价值和参考意义。

4. 全文精读分析

未进行全文分析，原因：非OA / 无法合法访问全文。

5. 一句话评价

该研究提出了纳米抗体工程化改造的新方法，为VHH稳定性/亲和力优化提供了可推广的技术路线。

三、本周重点趋势总结

1. 支架类型分布

• nanobody/VHH：3 篇
• affibody：2 篇
• 其他蛋白支架：1 篇

2. 应用方向热点

• 治疗应用：5 篇
• 工程化/设计：4 篇
• 诊断/成像：3 篇
• 结构解析：3 篇
• 筛选平台/方法：2 篇
• 神经疾病：2 篇
• 肿瘤治疗：1 篇
• 药物递送：1 篇
• 基础研究/其他：1 篇

3. 本周趋势洞察

诊断与检测平台创新：3 篇涉及诊断检测，纳米抗体在ELISA、生物传感器、免疫PET成像中持续扩展应用边界。

工程化与设计方法进展：4 篇涉及支架工程化改造，包括二硫键引入、亲和力成熟、多价展示平台等策略，反映了该领域从“发现”到“优化”的持续转变。

药物递送系统整合：1 篇将蛋白支架用于靶向递送，affibody-Ferritin纳米笼和纳米抗体-DNA折纸平台展示了多模态递送的新范式。

4. 值得关注的靶点、团队与技术路线

• 靶点：CD4（HIV基因编辑）、CLDN18.2（胃癌放疗）、BAFF-R（CAR-T）、EGFR（affibody/DARPin递送）、MR1（免疫调节）、IL-6Rα（自身免疫）
• 技术路线：DNA origami多价展示、SpyCatcher蛋白偶联、cell-penetrating peptide融合、纳米酶集成检测
• 值得追踪：纳米抗体在放射性配体治疗中的应用、双模块化CAR-T设计、细胞内蛋白递送系统

四、待核验或排除文献

以下文献因期刊分区无法核验或不满足纳入标准，未列入正式推荐清单：

此外，以下文献因主题不符被排除：

五、最终质量检查