首页|Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

Ultrasound-responsive spherical nucleic acid against c-Myc/PD-L1 to enhance anti-tumoral macrophages in triple-negative breast cancer progression

扫码查看
原文链接
  • 万方数据
  • 维普
Triple-negative breast cancer(TNBC)is the most challenging breast cancer subtype because of its aggressive behavior and limited ther-apeutic targets.c-Myc is hyperactivated in the majority of TNBC tissues,however,it has been considered an"undruggable"target due to its disordered structure.Herein,we developed an ultrasound-responsive spherical nucleic acid(SNA)against c-Myc and PD-L1 in TNBC.It is a self-assembled and carrier-free system composed of a hydrophilic small-interfering RNA(siRNA)shell and a hydrophobic core made of a peptide nucleic acid(PNA)-based antisense oligonucleotide(ASO)and a sonosensitizer.We accomplished significant enrichment in the tumor by enhanced permeability and retention(EPR)effect,the controllable release of effective elements by ultrasound activation,and the combination of targeted therapy,immunotherapy and physiotherapy.Our study demonstrated significant anti-tumoral effects in vitro and in vivo.Mass cytometry showed an invigorated tumor microenvironment(TME)characterized by a significant alteration in the composition of tumor-associated macrophages(TAM)and decreased proportion of PD-1-positive(PD-1+)T effector cells after appropriate treatment of the ultrasound-responsive SNA(USNA).Further experiments verified that tumor-conditioned macrophages residing in the TME were trans-formed into the anti-tumoral population.Our finding offers a novel therapeutic strategy against the"undruggable"c-Myc,develops a new targeted therapy for c-Myc/PD-L1 and provides a treatment option for the TNBC.

triple-negative breast cancerc-Mycspherical nucleic acidself-assembly

Runtian Wang、Gaigai Li、Fangyan Gao、Feng Xu、Xintong Li、Jian Zhang、Jinbo Li、Xiaoxiang Guan

展开 >

Department of Oncology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China

State Key Laboratory of Analytical Chemistry for Life Sciences,Jiangsu Key Laboratory of Advanced Organic Materials,School of Chemistry and Chemical Engineering,Chemistry and Biomedicine Innovation Center(ChemBIC),Nanjing University,Nanjing 210023,China

Department of Medical Oncology,Fudan University Shanghai Cancer Center//Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China

Jiangsu Key Lab of Cancer Biomarkers,Prevention and Treatment,Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing 211166,China

展开 >

国家自然科学基金国家自然科学基金国家自然科学基金Key Foundation for Social Development Project of Jiangsu Province of China

819201080292207706322322703BE2021741

2024

10.1007/s11427-023-2433-y

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子：0.806
ISSN：1674-7305
年,卷(期)：2024.67(4)
  • 52