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  3. Targeting pre-metastatic niche with inhalable dendritic cell vesicles to prevent breast cancer lung metastasis

Targeting pre-metastatic niche with inhalable dendritic cell vesicles to prevent breast cancer lung metastasis

  • J Nanobiotechnology. 2025 Dec 12;23(1):765. doi: 10.1186/s12951-025-03842-9.
Qingqing Leng 1 2,  Zhengxin Yu 1 2,  Yu Zhao 1 2,  Yue Shao 1 2,  Qiuyang Jin 1 2,  Qiyu Zhao 1 2,  Ying Yang 3 2,  Mengmeng Ji 3 4,  Hua Yang 4,  Lili Ren 4,  Guang Jia 3 2,  Xueyi Wang 5,  Jinchao Zhang 6 7,  Zhenhua Li 8,  Huifang Liu 9 10
Affiliations

Affiliations

  • 1 College of Pharmaceutical Science, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, 071002, China.
  • 2 State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, 071002, China.
  • 3 College of Chemistry & Materials Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, China.
  • 4 Affiliated Hospital of Hebei University, Baoding, 071000, China.
  • 5 The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, China.
  • 6 College of Chemistry & Materials Science, Chemical Biology Key Laboratory of Hebei Province, Hebei University, Baoding, 071002, China. [email protected].
  • 7 State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, 071002, China. [email protected].
  • 8 The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523059, China. [email protected].
  • 9 College of Pharmaceutical Science, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding, 071002, China. [email protected].
  • 10 State Key Laboratory of New Pharmaceutical Preparations and Excipients, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, Hebei University, Baoding, 071002, China. [email protected].
PMID: 41388289 DOI: 10.1186/s12951-025-03842-9
Abstract

Distant metastasis remains the primary cause of mortality in breast Cancer, yet therapeutic options to prevent or treat metastatic progression are still limited. Emerging evidence suggests that the formation of the pre-metastatic niche (PMN) serves as a pivotal step in the process of breast Cancer metastasis. Lung tissue is the major site of breast Cancer metastasis with elevated prostaglandin E2 (PGE2) levels, which fosters immunosuppression and promotes niche establishment. Although EP2 and EP4 receptor antagonists have shown promise in counteracting PGE2-driven immunosuppression, their clinical translation is hindered by poor selectivity and bioavailability. To address these limitations, we developed a nanotherapeutic platform using dendritic cell-derived nanovesicles (NVs) engineered with α-lactalbumin (α-LA) and loaded with the EP2 antagonist TG6-10-1 and the EP4 antagonist GW627368, termed L-TG/GW-NVs. L-TG/GW-NVs exploit the homing ability of DC-derived NVs and retain immune-stimulatory molecules, thereby preventing PMN formation by blocking PGE2 signaling and reactivating suppressed dendritic cells and cytotoxic T cells. This synergistic strategy markedly suppressed lung metastasis by disrupting niche formation, enhancing immune activation, and reversing T cell exhaustion. Collectively, our findings establish a novel framework for metastatic breast Cancer therapy and provide valuable insights for future translational studies and combinational immunotherapies.

Keywords

Dendritic cell dysfunction; Dendritic extracellular vesicle; Lung metastasis; Pre-metastatic niche; Prostaglandin E2 antagonists.

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