{"id":473,"title":"NanoPro – a Framework for Probiotically-Guided Nanovector Therapy","title_zh":"NanoPro：由益生菌递送肿瘤结合标签引导纳米载体治疗的体外验证框架","url":"https://doi.org/10.64898/2026.10.28.762486","doi":"10.64898/2026.10.28.762486","pmid":null,"journal":"bioRxiv","kind":"preprint","lang":"en","published_at":"2026-10-29T00:00:00+00:00","fetched_at":"2026-11-08T03:44:14+00:00","authors":["Michels A","Haseki A","Ashraf M","Lam A","Grant KR","Lu A","Vincent RL","Im J","Singer ZS","Ballister ER","Danino T"],"primary_topic":"repro-microbiome","topics":[{"slug":"endometrium","score":1.0,"hits":["placenta"]}],"topic_score":1.0,"preference_score":0.0,"preference_labels":[],"llm_score":30.0,"final_score":30.0,"score_dims":{"novelty":68,"rigor":45,"impact":12,"relevance":8,"translation":10},"recommend_reason":"该工作提出了以工程益生菌释放“ProTag”标签，使抗原特征不明显的肿瘤也能被纳米载体识别的思路，作为方法学探索有一定新意；但仅停留在体外细胞系验证，且属肿瘤纳米治疗领域，与生殖医学、辅助生殖及胚胎研究无实质关联，对本报读者价值很低。","keywords":["益生菌工程化","纳米载体靶向递送","ProTag 标签","肿瘤抗原问题","慢病毒载体","体外原理验证"],"selected":0,"story_id":null,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"europepmc-preprints","source_name":"Europe PMC · 预印本（领域内）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"biorxiv","journal_tier":"standard","journal_if":null,"is_mock":false,"summary_zh":"该预印本针对肿瘤靶向纳米治疗中的“抗原问题”——可用的受体靶向纳米载体种类多，但肿瘤表面可及的靶受体少——提出 NanoPro 平台：用工程化益生菌 Escherichai coli Nissle 1917 释放“ProTag”标签。ProTag 由正交抗原（GFP 或 ALFA）与胎盘生长因子-2 的肝素结合域融合而成，可借助肝素结合域（HBD）附着于细胞表面，充当纳米载体的对接受体；敲除 lpp 基因后，上清中 ProTag 浓度提高 16.5 倍，且不影响菌株活性。用含 ProTag 的上清孵育 MC-38 与 MDA-MB-468 肿瘤细胞后，再加入靶向 GFP/ALFA 的慢病毒载体，多数细胞被转导，抗原特异性分别达 96.5% 和 98.5%，且在 625 倍稀释下仍保持选择性。这仅为体外原理验证，与生殖医学无直接关联。","summary":"ABSTRACT The “antigen problem”, i.e. the disconnect between the broad spectrum of therapeutic modes enabled by the range of viral and synthetic nanoparticles for which workable receptor-targeting architectures exist and the relative dearth of addressable target receptors on most tumors, is a long-standing challenge in targeted tumor nanotherapy. Here we provide in vitro -proof-of-principle for NanoPro, a platform for guiding nanoscale therapeutics to otherwise antigenically indistinct tumors via probiotically-released tumor cell-binding tags, ProTags. These consist of an orthogonal antigen (GFP or ALFA) fused to the heparin-binding domain of placenta growth factor-2 and serve as attachment receptors for ProTag-targeted nanovectors. ProTag release from Escherichia coli Nissle 1917 was facilitated by deletion of the membrane-tethering lpp gene, which increased ProTag supernatant concentrations 16.5–fold compared to the parental strain without impacting viability. HBD-dependent decoration with ProTag in bacterial supernatant followed by treatment with receptor-targeted aGFP- or aALFA-lentiviral vectors resulted in majority transduction of MC-38 and MDA-MB-468 tumor cell lines with antigen specificities of 96.5% and 98.5%, respectively, depending on the choice of nanobody. This ProTag-mediated interaction was notably robust, with selective transduction still observed at 625–fold supernatant dilution, warranting further exploration of the utility of the NanoPro system for tumor-restricted delivery of nanotherapeutics.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}