Engineered mechanosensitive MSCs enable synthetic radiotheranostic targeting across tumor types.

Authors

Xiujie Yang, Qi Yin, Kui Li, Jianze Wang, Rui Song, Haoyi Zhou, Shu Han, Linyu Zhang, Yuwen Zeng, Da Xu, Feng Wang, Shixin Zhou, Yang Yang, Hua Zhu, Chunhong Zheng, Yang Li, Zhi Yang, Xing Yang, Zhaofei Liu

Published in

Cell stem cell. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

Radiopharmaceutical-based imaging and targeted radionuclide therapy are often limited by heterogeneous or absent molecular targets in tumors. Here, we present a stiffness-responsive mesenchymal stem cell (MSC)-assisted relayed tumor-targeting (SMART) platform that converts matrix stiffness into a programmable molecular entry point for radiotheranostics. Engineered MSCs sense elevated mechanical stiffness within the tumor microenvironment and induce localized expression of synthetic biomarkers, thereby enabling radiopharmaceutical targeting independent of endogenous target availability. As a proof of concept, SMART-driven expression of prostate-specific membrane antigen (PSMA) enables sensitive tumor detection by ⁶⁸Ga-PSMA-617 positron emission tomography (PET) and effective treatment with ¹⁷⁷Lu-AB-PSMA-617 across multiple tumor models, with improved sensitivity and reduced off-target uptake compared with conventional ¹⁸F-fluorodeoxyglucose PET. This platform is readily adaptable to alternative synthetic targets and induced pluripotent stem cell (iPSC)-derived MSCs. By translating a universal physical feature of tumors into an actionable molecular signature, SMART expands the scope of precision radiotheranostics beyond native biomarkers.

PMID:
42624106
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.