Photodynamic therapy (PDT) is a highly promising therapeutic modality for cancer treatment. The development of stimuli‐responsive photosensitizer nanomaterials overcomes certain limitations in clinical PDT. Herein, we report the rational design of a highly sensitive PEGylated photosensitizer‐peptide nanofiber (termed PHHPEG6 NF) that selectively aggregates in the acidic tumor and lysosomal microenvironment. These nanofibers exhibit acid‐induced enhanced singlet oxygen generation, cellular uptake, and PDT efficacy in vitro, as well as fast tumor accumulation, long‐term tumor imaging capacity and effective PDT in vivo. Moreover, based on the prolonged presence of the fluorescent signal at the tumor site, we demonstrate that PHHPEG6 NFs can also be applied for prognostic monitoring of the efficacy of PDT in vivo, which would potentially guide cancer treatment. Therefore, these multifunctional PHHPEG6 NFs allow control over the entire PDT process, from visualization of photosensitizer accumulation, via actual PDT to the assessment of the efficacy of the treatment.
IntroductionIt is considered that Tupaia chinensis can replace laboratory primates in the study of nervous system diseases. To date, however, protein expression in the brain of Tupaia chinensis has not been fully understood.MethodThree age groups of T. chinensis-15 days, 3 months and 1.5 years—were selected to study their hippocampal protein expression profiles.ResultsA significant difference was observed between the 15-day group and the other two age groups, where as there were no significant differences between the 3-month and 1.5-year age groups. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that differentially expressed proteins could be enriched in several pathways related to neurovascular diseases, such as metabolic pathways for Alzheimer's disease (AD), Huntington's disease, Parkinson's disease, and other diseases. The KEGG enrichment also showed that relevant protein involved in oxidative phosphorylation in the hippocampus of T. chinensis for 15days were downregulated, and ribosomal proteins (RPs) were upregulated, compared to those in the hippocampus of the other two age groups.DiscussionIt was suggested that when the hippocampus of T. chinensis developed from day 15 to 3 months, the expression of oxidatively phosphorylated proteins and RPs would vary over time. Meanwhile, the hippocamppal protein expression profile of T. chinensis after 3 months had become stable. Moreover, the study underlines that, during the early development of the hippocampus of T. chinensis, energy demand increases while protein synthesis decreases. The mitochondria of T. chinensis changes with age, and the oxidative phosphorylation metabolic pathway of mitochondria is closely related to neurovascular diseases, such as stroke and cerebral ischemia.
Photodynamic therapy (PDT) is a highly promising therapeutic modality for cancer treatment. The development of stimuli-responsive photosensitizer nanomaterials overcomes certain limitations in clinical PDT. Herein, we report the rational design of a highly sensitive PEGylated photosensitizer-peptide nanofiber (termed PHHPEG 6 NF) that selectively aggregates in the acidic tumor and lysosomal microenvironment. These nanofibers exhibit acid-induced enhanced singlet oxygen generation, cellular uptake, and PDT efficacy in vitro, as well as fast tumor accumulation, long-term tumor imaging capacity and effective PDT in vivo. Moreover, based on the prolonged presence of the fluorescent signal at the tumor site, we demonstrate that PHHPEG 6 NFs can also be applied for prognostic monitoring of the efficacy of PDT in vivo, which would potentially guide cancer treatment. Therefore, these multifunctional PHHPEG 6 NFs allow control over the entire PDT process, from visualization of photosensitizer accumulation, via actual PDT to the assessment of the efficacy of the treatment.
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