DNA Molecular Robot for Osteosarcoma Therapy and Bone Regeneration.

Authors

Junbo Dang, Panqi Sun, Junhui Jiang, Tianhao Zhao, Ruifu Lv, Hongbo Wang, Minna Ma, Dahui Sun, Mei Zhang

Published in

Biomacromolecules. Volume 27. Issue 9. Pages 5861-5877. Sep 14, 2026.

Abstract

Preventing tumor recurrence while promoting bone regeneration remains a major challenge for osteosarcoma implants after limb-salvage surgery. Herein, we developed a DNA molecular robot (DMR) that converts tumor microenvironment (TME) and near-infrared (NIR) stimuli into integrin-mediated mechanical forces, generating microtubule-targeting activity without drugs. The DNA-polypeptide chimera contains RGD peptides for integrin anchoring and allosteric DNA switches with tunable piconewton sensitivity. Under acidic TME and NIR irradiation, DMR modulates microtubule dynamics, suppresses adhesion protein expression through the FAK-Src pathway, and disrupts mitotic spindle formation. Consequently, DMR selectively eliminates osteosarcoma cells, reducing tumor volume by 81.5%, while simultaneously enhancing bone regeneration with a 2.1-fold increase in trabecular thickness. By transducing integrin-mediated forces into intracellular microtubule regulation, DMR provides a nonpharmacological strategy for dual-functional implants with synergistic antitumor and osteogenic activities.

PMID:
42734289
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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