Affiliation:
1. State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and Devices School of Biological Sciences and Medical Engineering Southeast University Nanjing 210096 P. R. China
Abstract
AbstractUniversal chemotherapy in glioblastoma patients causes chemoresistance and further limits immune cells by creating an immunosuppressive tumor microenvironment that are difficult to solve by single‐drug therapeutic approaches. Here, this work designs hybrid drug‐loaded nanoliposomes by co‐loading the chemotherapeutic drug temozolomide (TMZ) and nitric oxide (NO) prodrug JS‐K with sphingosine‐1‐phosphate molecules (S1P) on the surface. The S1P‐S1P receptors axis endows nanoliposomes with rapid targeting and lysosomal escaping capability. Then, fine‐tuned TMZ release and NO gas production following JS‐K release in glioma microenvironment decrease chemoresistance and increase tumor immunogenicity through inhibiting the cellular autophagy as well as inducing mitochondrial dysfunction. RNA sequencing analysis demonstrates that the NO gas generation reprograms glioma microenvironment immune and inflammation‐related pathways. The positive immune response in turn effectively activates the enhanced efficacy of chemotherapy. NO gas generated nanoliposomes thus have attractive paradigm‐shifting applications in the treatment of “cold” tumors across a range of immunosuppressive indications.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
China Postdoctoral Science Foundation
Fundamental Research Funds for the Central Universities
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献