Delivery of nitric oxide with a nanocarrier promotes tumour vessel normalization and potentiates anti-cancer therapies

Yun Chieh Sung, Pei Ru Jin, Li An Chu, Fu Fei Hsu, Mei Ren Wang, Chih Chun Chang, Show Jen Chiou, Jiantai Timothy Qiu, Dong Yu Gao, Chu Chi Lin, Yu Sing Chen, Yi Chiung Hsu, Jane Wang, Fu Nien Wang, Pei Lun Yu, Ann Shyn Chiang, Anthony Yan Tang Wu, John Jun Sheng Ko, Charles Pin Kuang Lai, Tsai Te LuYunching Chen

Research output: Contribution to journalArticlepeer-review

278 Citations (Scopus)


Abnormal tumour vasculature has a significant impact on tumour progression and response to therapy. Nitric oxide (NO) regulates angiogenesis and maintains vascular homeostasis and, thus, can be delivered to normalize tumour vasculature. However, a NO-delivery system with a prolonged half-life and a sustained release mechanism is currently lacking. Here we report the development of NanoNO, a nanoscale carrier that enables sustained NO release to efficiently deliver NO into hepatocellular carcinoma. Low-dose NanoNO normalizes tumour vessels and improves the delivery and effectiveness of chemotherapeutics and tumour necrosis factor-related, apoptosis-inducing, ligand-based therapy in both primary tumours and metastases. Furthermore, low-dose NanoNO reprogrammes the immunosuppressive tumour microenvironment toward an immunostimulatory phenotype, thereby improving the efficacy of cancer vaccine immunotherapy. Our findings demonstrate the ability of nanoscale NO delivery to efficiently reprogramme tumour vasculature and immune microenvironments to overcome resistance to cancer therapy, resulting in a therapeutic benefit.

Original languageEnglish
Pages (from-to)1160-1169
Number of pages10
JournalNature Nanotechnology
Issue number12
Publication statusPublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • General Materials Science
  • Condensed Matter Physics
  • Electrical and Electronic Engineering


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