2. Academic Validation
  3. Ultrasound-Responsive Cerasome Nanoparticle Improves STING-Driven Immunotherapy in Triple-Negative Breast Cancer

Ultrasound-Responsive Cerasome Nanoparticle Improves STING-Driven Immunotherapy in Triple-Negative Breast Cancer

  • ACS Appl Mater Interfaces. 2026 Feb 18;18(6):9379-9400. doi: 10.1021/acsami.5c21141.
Di Yang 1,  Chao Sun 1,  Yu He 1,  Ruiqi Wu 2,  Chenhui Li 3,  Xuantong Gong 1,  Haiming Zhuang 1,  Yan Wang 4,  Hao Qin 5,  Yan Wang 5,  Qian Li 3,  Ramasamy Paulmurugan 6,  Xiaolong Liang 2,  Yong Wang 1 4
Affiliations

Affiliations

  • 1 Department of Ultrasound, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 2 Department of Ultrasound, Peking University Third Hospital, Beijing 100096, China.
  • 3 Department of Ultrasound, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, China.
  • 4 Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110801, China.
  • 5 Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
  • 6 Department of Radiology, Stanford University, Palo Alto, California 94305, United States.
PMID: 41660697 DOI: 10.1021/acsami.5c21141
Abstract

Immunotherapy shows promise for triple-negative breast Cancer (TNBC), yet its effectiveness is restricted by low response rates, poor immune cell infiltration, and systemic side effects. Here, an ultrasound-responsive cerasomal nanoplatform integrating a STING agonist (SR-717@PC-iRGD) is developed for synergistic sonodynamic-immunotherapy. The nanocarrier is self-assembled from cerasome-forming lipids (CFL), porphyrin-conjugated lipids (PL), unsaturated Phospholipids (DOPC), DSPC, and DSPE-PEG2000-iRGD, with SR-717 loaded in the lipid bilayer. The resulting assembly yields nanoparticles (NPs) with high SR-717 loading and exceptional stability. The siloxane shell (cerasome) confers high stability and prevents premature drug leakage, while iRGD promotes nanoparticle binding to tumor specific Integrin to facilitate accumulation and retention in the tumor. Upon ultrasound irradiation, porphyrin generates Reactive Oxygen Species (ROS) that oxidize the lipid bilayer and disrupt the cerasome, enabling on-demand SR-717 release at tumor site. The released SR-717 activates the STING pathway, driving type-I interferon production, dendritic cell maturation, and CD8+ T-cell infiltration. This strategy integrates sonodynamic therapy (SDT) with localized immune activation, addressing challenges of instability and inefficient delivery. The platform thus offers a precise and effective approach to stimulate antitumor immunity and enhance therapeutic outcomes for TNBC where no tumor targeted therapy is currently available.

Keywords

STING agonist; cerasome nanoparticles; immunotherapy; triple-negative breast cancer; ultrasound.

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