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Construction And Application Of PH&NIR Responsive Multi-functional Theranostic Nanoplatform

Posted on:2021-03-25Degree:MasterType:Thesis
Country:ChinaCandidate:W X ZhuFull Text:PDF
GTID:2492306122981449Subject:Materials engineering
Abstract/Summary:
The conventional tumor therapeutic strategies including surgery,chemotherapy and radiotherapy,exhibit obvious disadvantages,such as low efficiency and systemic toxicity.With the rapid development of nanotechnology,various theranostic platforms based on nanomaterials have been extensively applied in the biomedical field.To address these issues in cancer therapy,collaborative treatments have been developed,which is able to fully take advantage of synergy for enhanced anti-tumor effect.In the current study,we designed and synthesized multifunctional nanocarriers for photochemotherapy applications,and the details are clarified as follows:1)In the second chapter,we discussed the synthesis method of DOX/Pd@ZIF-8@PDA nanoparticles and their application in tumor treatment.DOX/Pd@ZIF-8 nanoparticles were synthesized by using one-pot method,then modified with polydopamine to improve its biocompatibility.Cell internalization showed that DOX/Pd@ZIF-8@PDA nanomaterials could effectively enter tumor cells.The nanoparticles exhibit excellent photothermal efficiency and photothermal stability under the excitation of a near-infrared laser.In an acidic environment(p H=5.7),the material releases about 67% of the DOX after being irradiated by near-infrared laser for 30 minutes,which allows a p H and NIR dual stimulating drug release.Cytotoxicity experiments have shown that this combined photochemotherapy exhibits higher efficiency than monotherapy in tumor treatment.2)In the third chapter,we analyzed the therapy efficiency of DOX/Pd@ZIF-8@PDA nanoparticles on mice xenograft model.Photoacoustic imaging results show that DOX/Pd@ZIF-8@PDA nanoparticles can be used as a photoacoustic contrast agent,which can image the tumor site after intratumoral injection.Finally,the BALB/c mice bearing tumor was used to verify the treatment effect of photochemotherapy.Our experiment showed that tumor size of mice in the experimental group was almost zero and did not relapse for a long time.The main organs of the mice in the photochemotherapy group were analyzed by using H&E staining,and no significant indication of toxicity was determined.In short,this nanoparticle could be developed as a promising antitumor therapy.3)The fourth chapter presents the synthesis of DOX@HMCN-PEG nanoparticles and their antitumor effects.The nanoparticles have uniform morphology features and size,hollow mesoporous structure and excellent drug loading capacity.The excitation of near-infrared laser induced obvious photothermal heating effect of the nanoparticles.The nanoparticles facilitate drug release under the dual response of p H & NIR.The results of cell uptake studies showed a pronounced effect of 4T1 cells on the uptake of the nanoparticles.Finally,the anti-tumor effect of DOX@HMCN-PEG nanoparticles was investigated by using 4T1 cells.The combined therapy group showed an excellent anti-tumor effect,reaching the cell survival ratio of as high as 20%.Therefore,the hollow mesoporous carbon sphere,as a drug carrier,shows huge potential in anti-tumor therapy.
Keywords/Search Tags:Tumor, Photoacoustic imaging, Photothermal therapy, Chemotherapy, Combination therapy
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