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Near-Infrared Light Regulation Of Tumor PI3K/Akt Signaling Pathway For Enhancing Cancer Cell Apoptosis Through Conjugated Polymer Nanoparticles

Posted on:2021-09-25Degree:MasterType:Thesis
Country:ChinaCandidate:B K BaoFull Text:PDF
GTID:2504306557998199Subject:Biophysics
Abstract/Summary:
Conjugated polymer nanoparticles(CPNs)are nanomaterials formed by assembling conjugated polymers(CPs)with amphiphilic polymers.CPNs not only have excellent optoelectronic properties,but also have good biocompatibility and photostability due to their diverse structure and functional design.The PI3 K / Akt signaling pathway plays an important regulatory role in tumor cells and controls tumor cell proliferation and apoptosis.Under the mediation of calmodulin(Ca M),the use of CPNs to regulate this signaling pathway can induce cancer cells to apoptosis.This paper focuses on the design,preparation and biological application of near-infrared conjugated polymer nanoparticles in the following aspects:1.Conjugated polymer nanoparticles(CPNs-C)with excellent photothermal effect were synthesized.And co-precipitation method was used to prepare PDPP and dipalmitoyl phosphatidylethanolamine-polyethylene glycol-maleimide(DSPE-PEG2000-MAL)into CPNs.Modified the surface of CPNs with calmodulin antibody to construct a new type of specific conjugated polymer nanoparticles(CPNs-C),and applied it to photothermally induced cancer cell apoptosis in the near infrared light.CPNs and CPNs-C were characterized by dynamic light scattering experiments(DLS),UV absorption spectrum analysis,photothermal conversion capability analysis,light stability analysis,and near-infrared thermal imaging experiments.The particle sizes of CPNs and CPNs-C are similar,but the electrical properties of CPNs-C have changed greatly under the action of Ca M antibodies.They both have strong photothermal conversion ability,can reach higher temperature in a short time,and both have high structural stability and show good light stability.In addition,CPNs-C has specificity and higher biocompatibility relative to CPNs,overcomes the shortcomings of CPNs without selectivity and orientation,and lays the foundation for the application of conjugated polymers at the biological level.2.Explore the killing ability and mechanism of CPNs and CPNs-C to cancer cells under near-infrared light.It was verified that specific CPNs-C can induce apoptosis of cancer cells by regulating the PI3K/Akt signaling pathway.CPNs-C not only has a good photothermal effect,but also inhibits the phosphorylation of protein kinase B(Akt)and phosphatidylinositol 3-kinase(PI3K)through binding to Ca M.This makes Akt unable to dock on the cell membrane,which changes the phosphorylation of proteins downstream of the signaling pathway and promotes apoptosis of cancer cells.Cells treated with CPNs and CPNS-C were tested for cell viability,laser confocal microscopy,flow cytometry,and Western blot and analyzed.The degree of phosphorylation of Fox O3 a protein increased in cells treated with CPNs-C,and the degree of phosphorylation of Akt p308,Akt p473,and GSK-3β proteins was significantly reduced.Compared with the photothermal effect of traditional CPNs,CPNs-C can significantly improve the killing effect on cancer cells by regulating signal pathways.The synergistic effect of photothermal treatment and induced apoptosis in the killing of cancer cells is realized,and a more efficient scheme for cancer cell treatment is provided.
Keywords/Search Tags:Calmodulin, Conjugated polymer nanoparticles, Photothermal therapy, PI3K/Akt signaling pathway, Cancer cell apoptosis
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