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Universal 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.
Pubmed ID: 37085663
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Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsMulti-threaded software for rapid quality control and preprocessing of high throughput sequencing data specified for different experiments. It consists of four modules that speed up the report on statistics graphs of raw datasets, preprocessed datasets and preprocessing status.
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsCell line HT22 is a Transformed cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line GL261 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionslaboratory mouse with name BALB/cAnNCrl from MGI.
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