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

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...

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Vydáno v:Nature nanotechnology Ročník 14; číslo 12; s. 1160 - 1169
Hlavní autoři: Sung, Yun-Chieh, Jin, Pei-Ru, Chu, Li-An, Hsu, Fu-Fei, Wang, Mei-Ren, Chang, Chih-Chun, Chiou, Show-Jen, Qiu, Jiantai Timothy, Gao, Dong-Yu, Lin, Chu-Chi, Chen, Yu-Sing, Hsu, Yi-Chiung, Wang, Jane, Wang, Fu-Nien, Yu, Pei-Lun, Chiang, Ann-Shyn, Wu, Anthony Yan-Tang, Ko, John Jun-Sheng, Lai, Charles Pin-Kuang, Lu, Tsai-Te, Chen, Yunching
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.12.2019
Témata:
Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - therapeutic use
Angiogenesis
Animals
Apoptosis
Blood vessels
Cancer
Cancer therapies
Cancer vaccines
Carcinoma, Hepatocellular - blood supply
Carcinoma, Hepatocellular - drug therapy
Controlled release
Delayed-Action Preparations - chemistry
Drug delivery systems
Hepatocellular carcinoma
Homeostasis
Humans
Immunostimulation
Immunotherapy
Liver cancer
Liver Neoplasms - blood supply
Liver Neoplasms - drug therapy
Male
Metastases
Mice
Microenvironments
Nanoparticles - chemistry
Neovascularization, Pathologic - drug therapy
Nitric oxide
Nitric Oxide - administration & dosage
Nitric Oxide - therapeutic use
Phenotypes
Sustained release
Therapy
Tumor microenvironment
Tumor Microenvironment - drug effects
Tumor necrosis factor
Tumors
ISSN:1748-3387, 1748-3395, 1748-3395
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
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ISSN:1748-3387
1748-3395
1748-3395
DOI:10.1038/s41565-019-0570-3