DNA Molecular Robot for Osteosarcoma Therapy and Bone Regeneration

IF 5.9 2区化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomacromolecules Pub Date : 2026-09-14 Epub Date: 2026-09-17 DOI:10.1021/acs.biomac.5c02333

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

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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.

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查看原文本刊更多论文

骨肉瘤治疗和骨再生的DNA分子机器人

在促进骨再生的同时防止肿瘤复发仍然是骨肉瘤植体在保肢手术后面临的主要挑战。在此，我们开发了一种DNA分子机器人（DMR），它将肿瘤微环境（TME）和近红外（NIR）刺激转化为整合素介导的机械力，在没有药物的情况下产生微管靶向活性。DNA -多肽嵌合体含有用于整合素锚定和具有可调皮牛顿灵敏度的变构DNA开关的RGD肽。在酸性TME和NIR照射下，DMR调节微管动力学，通过fak - src途径抑制粘附蛋白的表达，并破坏有丝分裂纺锤体的形成。因此，dmr选择性地消除骨肉瘤细胞，使肿瘤体积减少81.5%，同时增强骨再生，使骨小梁厚度增加2.1倍。通过将整合素介导的力量转化为细胞内微管调节，DMR为具有协同抗肿瘤和成骨活性的双重功能植入物提供了一种非药物策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomacromolecules 化学-高分子科学

CiteScore

10.60

自引率

4.80%

发文量

417

审稿时长

1.6 months

期刊介绍： Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.