期刊
ACS APPLIED MATERIALS & INTERFACES
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c15882
关键词
nitric oxide; metastasis; anticoagulation; nanotechnology; supramolecular interactions
资金
- National Key Research and Development Program of China
- National Natural Science Foundation of China
- [2020YFE0204400]
- [52022090]
A glutathione-sensitive supramolecular nanocarrier is developed for the delivery of nitric oxide (NO) and the chemotherapeutic agent gemcitabine (GEM). This nanocarrier effectively inhibits tumor cell-induced platelet aggregation (TCIPA) and attenuates the migration and invasion of tumor cells. In vivo experiments demonstrate that the nanocarrier suppresses primary tumor growth and significantly inhibits tumor metastasis.
Tumor cell-induced platelet aggregation (TCIPA) is known as a critical step in hematogenous tumor metastasis. The endogenous nitric oxide (NO) plays an important role in anticoagulation, which might have great potential to inhibit TCIPA. Herein, a glutathione-sensitive supramolecular nanocarrier is prepared via host-guest interaction for effective delivery of NO and chemotherapeutic agent gemcitabine (GEM). NO could be effectively released in tumor cells and inhibits platelet activation and aggregation. The inhibition of TCIPA by NO could effectively attenuate the migration and invasion of tumor cells in vitro. Furthermore, the in vivo experiments demonstrate that the NO and GEM co-delivered supramolecular nanocarriers can suppress the growth of primary tumor. More importantly, although NO-containing nanocarriers cannot inhibit the growth of primary tumors effectively, they can significantly inhibit tumor metastasis. This NO-based nano-delivery system not only provides new inspiration for multifunctional applications of NO in cancer therapy but also shows great potential in clinical antimetastatic applications.
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