Evidence map›Paper›PMID 41267074›Full record

ArticleJournal of translational medicine2025

De novo design of a two-step approach targeting Claudin-6 for enhanced drug delivery to solid tumors.

Jiayao Yan, Liqing Zhong, Xiaotong Chen, Lin Li, Fangcen Liu, Lei Lei, Mengchao An, Xiao Wei, Ying Wang, Tianran Chen and 7 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jiayao Yan *Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Liqing Zhong *Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Xiaotong ChenDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Lin LiDepartment of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Fangcen LiuDepartment of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Lei LeiZhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Mengchao AnThe Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
Xiao WeiDepartment of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Ying WangDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Tianran ChenDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Jingyi GuoDepartment of Oncology, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China.
Jie ShaoDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Xiaoxiao YuSchool of Life Sciences, Nanjing University, Nanjing, China.
Yingjie ZhaoDepartment of Biology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
Rutian LiDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. rutianli@nju.edu.cn.
Qin LiuDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. liuqin@nju.edu.cn.
Baorui LiuDepartment of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. baoruiliu@nju.edu.cn.ORCID 0000-0002-2539-7732

Funding

Jiangsu Province Key Research and Development Program grant BE2023654Jiangsu Provincial Medical Key Discipline grant ZDXK202233Natural Science Foundation of China grant 82272811
6 · The paper itself

Abstract

backgroundAlthough antibody-conjugated drugs have achieved success in clinical practice for cancer treatment, challenges remain in developing a highly efficient drug delivery system with specific accumulation in tumors and reduction in side effects. With improved pharmacokinetics, strong covalent bonding and quick binding reactions, a pre-targeting approach via molecular pairs represents an attractive platform for two-step delivery system construction.

methodsBioinformatics and immunohistochemistry assays were performed to assess Claudin-6 (CLDN6) as a highly specific tumor target in solid tumors. A phage-displayed library was used to screen and optimize anti-CLDN6 designed ankyrin repeat proteins (DARPins), which were incorporated into a two-step delivery system based on SpyTag/SpyCatcher. Fluorescent staining, flow cytometry and near-infrared imaging were performed to assess the tumor-targeting ability and biodistribution of this delivery system. The cytotoxic drug, Monomethyl auristatin E (MMAE), was conjugated with the delivery system to evaluate its anti-tumor efficacy and safety profile.

resultsAnti-CLDN6 DARPins exhibited specific binding to CLDN6

conclusionsOur study presented the de novo design of a two-step drug delivery system targeting Claudin-6 with enhanced anti-tumor efficacy and improved biosafety. These findings highlighted the potential of this approach to enhance the efficacy of tumor-targeting therapies and reduce adverse effects, paving the way for more effective cancer treatments.

Indexed as

ClaudinsDrug Delivery SystemsDrug DesignNeoplasmsAnimalsCell Line, TumorFemaleHumansMiceOligopeptidesTissue DistributionXenograft Model Antitumor Assaysclaudin 6ClaudinsOligopeptidesCLDN6DARPinsPhage displayPre-targeting

Identifiers

PMID41267074
PMCPMC12632142

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.