中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy

文献类型：期刊论文

作者Yin, Lixuan5,6,7; Fu, Zirang7; Wang, Mengmeng5,6; Liu, Bo4; Sun, Xujie5,6,7; Liu, Kaiyue5,6,7; Feng, Xiaolong3,7; He, Zongyan7; Wang, Yutong7; Hou, Jiazhen7
刊名ACTA BIOMATERIALIA
出版日期2025-02-01
卷号193页码:498-513
关键词Triple-negative breast cancer Docetaxel Prodrug nanoparticle ROR1 siRNA pH responsive
ISSN号1742-7061
DOI10.1016/j.actbio.2024.12.055
英文摘要Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis. However, clinical application of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this study, the docetaxel (DTX) prodrug nanoparticle BBRM delivering ROR1 siRNA was constructed. The BBRM could be effectively internalized by tumor cells and endosomal escape to release DTX and ROR1 siRNA. In 4T1 tumor- bearing mice, BBRM could be targeting delivered to tumor and lung tissues, with good biosafety, achieving a tumor inhibition rate of 74.1 % and inhibiting lung metastasis. By integrating chemotherapy and RNA interference therapy, BBRM successfully co-delivered chemotherapeutic agents and siRNA to improve the therapeutic efficacy of triple-negative breast cancer and provided a promising strategy for clinical transformation. Statement of significance: Chemotherapy is still the primary treatment for triple-negative breast cancer (TNBC) after surgery ablation, but it causes side effects without targeting capacity. ROR1 is significantly expressed in TNBC cells, and RNA interference for ROR1 can suppress ROR1 gene expression to inhibit tumor proliferation. However, as oligonucleotides, effect of ROR1 siRNA is limited by susceptibility to clearance and difficulty in endosomal escape. In this work, we designed a nanodevice based on a docetaxel (DTX) prodrug that targets ROR1 for the synergistic therapy of TNBC. We constructed a nanoparticle (BBRM) for co-delivery of the DTX and ROR1 siRNA. The BBRM could be effectively internalized by tumor cells and endosomal escape. The ROR1 siRNA downregulated ROR1 protein expression and improved the anti-proliferative and anti-metastatic effects. In addition, BBRM reversed the immunosuppressive tumor microenvironment, thus improving breast cancer therapeutic efficacy. It was a pioneering investigation in synergistic chemo-gene therapy by co-delivering DTX and ROR1 siRNA for TNBC treatment.
资助项目National Key R & D Program of China[2022YFC3401404] ; Lingang Laboratory (Startup Fund), Shanghai Post-doctoral Excellence Program[2023017] ; Science and Technology Innovation Action Plan Sailing Plan of Shanghai[22YF1460500]
WOS研究方向Engineering ; Materials Science
语种英语
WOS记录号WOS:001421256500001
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/316206]  
专题新药研究国家重点实验室
通讯作者Li, Yaping; Lang, Tianqun
作者单位1.Jinan Univ, Coll Pharm, Guangdong Basic Res Ctr Excellence Nat Bioact Mol, State Key Lab Bioact Mol & Druggabil Assessment, Guangzhou 511436, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.East China Normal Univ, Sch Pharm, Shanghai 200062, Peoples R China
4.Univ Chicago, Dept Med, Biol Sci Div, Sect Genet Med, Chicago, IL 60637 USA
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Lingang Lab, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Yin, Lixuan,Fu, Zirang,Wang, Mengmeng,et al. A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy[J]. ACTA BIOMATERIALIA,2025,193:498-513.
APA Yin, Lixuan.,Fu, Zirang.,Wang, Mengmeng.,Liu, Bo.,Sun, Xujie.,...&Lang, Tianqun.(2025).A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy.ACTA BIOMATERIALIA,193,498-513.
MLA Yin, Lixuan,et al."A prodrug nanodevice co-delivering docetaxel and ROR1 siRNA for enhanced triple negative breast cancer therapy".ACTA BIOMATERIALIA 193(2025):498-513.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。