2. Academic Validation
  3. Self-Assembled Tetrahedral Framework Nucleic Acids Alleviate Pulmonary Hypertension by Regulating Calcium Homeostasis

Self-Assembled Tetrahedral Framework Nucleic Acids Alleviate Pulmonary Hypertension by Regulating Calcium Homeostasis

  • Adv Healthc Mater. 2025 Aug 11:e02810. doi: 10.1002/adhm.202502810.
Lin Yang 1,  Wenjing Hou 2,  Jie Lan 3,  Ruxia Liu 4,  Liujie Zhao 1,  Cai Zhang 5,  Dianxun Fu 6,  Haifang Yin 7 8 9,  Dong Li 1,  Shao-Kai Sun 10,  Jiaojiao Yu 10
Affiliations

Affiliations

  • 1 Department of Radiology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, China.
  • 2 Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research, Center for Cancer, Tianjin, 300060, China.
  • 3 Department of Bioinformatics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.
  • 4 Department of Rehabilitation, Division of Medical Technology, Tianjin Medical University, Tianjin, 300203, China.
  • 5 Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Centre of Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, China.
  • 6 Department of Radiology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 7 School of Medical Laboratory, Division of Medical Technology, Tianjin Medical University, Tianjin, 300203, China.
  • 8 Tianjin Key Laboratory of Cellular Homeostasis and Human Diseases, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Cell Biology, Tianjin Medical University, Tianjin, 300070, China.
  • 9 Department of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, China.
  • 10 School of Medical Imaging, Division of Medical Technology, Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin, 300203, China.
PMID: 40785539 DOI: 10.1002/adhm.202502810
Abstract

Pulmonary hypertension (PH) is a life-threatening Cardiovascular Disease characterized by cellular hyperproliferation and vascular remodeling, leading to heart failure. Unfortunately, effective and safe treatments remain strikingly deficient across basic research and clinical applications. Tetrahedral framework nucleic acids (tFNAs), with superior biocompatibility and versatile cellular regulatory capabilities, offer a promising therapeutic strategy for PH. Herein, a novel strategy for treating PH using tFNAs by regulating calcium homeostasis is presented. The synthesized tFNAs, which display ultra-small size, robust stability, and good biocompatibility, exhibit enhanced cellular uptake in pulmonary artery smooth muscle cells and markedly suppress their proliferation and migration. In the PH model, pulmonary arterial (PA) structural-functional analysis reveals that tFNAs significantly improve pulmonary artery acceleration time, reduce vascular wall thickness, and decrease α-SMA and PCNA expression. Cardiac structural-functional assessments, including treadmill tests, Sirius Red staining, and Masson's trichrome staining, show that tFNAs remarkably enhance exercise capacity, reduce the Fulton index, and alleviate right ventricular (RV) fibrosis. Transcriptomic and biochemical analyses reveal that tFNAs upregulate SERCA2a, downregulate VEGFD, restore calcium homeostasis, and modulate the PI3K-Akt pathway, thus ameliorating PA and RV remodeling. This study presents a novel DNA nanomaterial-based strategy for PH treatment and establishes a mechanistic foundation for future clinical applications.

Keywords

calcium signaling pathway; pulmonary artery smooth muscle cells; pulmonary hypertension; tetrahedral framework nucleic acids; vascular remodeling.

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