Designing targeted-delivering and stimuli-responsive nanocarriers for photodynamic therapy (PDT) is an appealing method, especially, targeting delivery of photosensitizers to mitochondria as the most sensitive cellular organelles to reactive oxygen species (ROS) could significantly enhance the therapeutic efficacy of PDT. In this study, we synthesized triphenylphosphonium bonded PEG-NH2 (TPP-PEG-NH2) and bridged to chlorin e6 (Ce6) via thioketal (TK) linkage to obtain red light-triggered, amphiphilic copolymer (TPP-PEG-TK-Ce6), which could self-assemble into micelles with an average size of 160 nm and zeta potential of +20.1 mV. The in vitro release behavior of TPP-PEG-TK-Ce6 nanocarriers showed a light-activated way and was dependent on the H2O2 concentration. TPP-PEG-TK-Ce6 nanocarriers exhibited high cytotoxicity against C6 cells with illumination. Confocal laser scanning microscopy observation indicated that TPP-PEG-TK-Ce6 nanocarriers were efficiently internalized into the mitochondrion of C6 cells, released Ce6 via light activated. By contrast, in the case of TPP-PEG-NH2 directly bonded Ce6 (TPP-PEG-Ce6) nanocarriers, little Ce6 was found in the mitochondrion. The stronger fluorescence in the mitochondrion of TPP-PEG-TK-Ce6 nanocarriers originated from the mitochondrial-targeting capability of TPP and the cleavage of TK linkages activated by light irradiation, which greatly improved the cellular uptake of TPP-PEG-TK-Ce6 nanocarriers and released more Ce6 in the mitochondrion. This work provided a facile strategy to improve PDT efficacy.
The purpose of the present study was to identify potential markers of local dorsal root ganglion (DRG) inflammation to aid diagnosis, treatment and prognosis evaluation of DRG pain. A localized inflammation of the DRG (LID) rat model was used to study the contribution of inflammation to pain. The dataset GSE38859 was obtained from the Gene Expression Omnibus database. Pre-treatment standardization of gene expression data for each experiment was performed using the R/Bioconductor Limma package. Differentially expressed genes (DEGs) were identified between a LID model and a sham surgery control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs and gene set enrichment analysis (GSEA) were carried out using the 'clusterProfiler' package in R. Using the Search Tool for Retrieval of Interacting Genes, a protein-protein interaction network was constructed and visualized. Candidate genes with the highest potential validity were validated using reverse transcription-quantitative PCR and western blotting. In total, 66 DEGs were enriched in GO terms related to inflammation and the immune response processes. KEGG analysis revealed 14 associated signaling pathway terms. Protein-protein interaction network analysis revealed 9 node genes, 3 of which were among the top 10 DEGs. Matrix metallopeptidase 9, chemokine CXCL9, and complement component 3 were identified as key regulators of DRG inflammatory pain progression.
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