Synthesis Of IHIC/ITIC@?-DOPE And Its Application In Photothermal And Photoacoustic Dual-mode Therapy

Cancer has been closely watched by people because of its high prevalence and fatality rate.In recent years,scientists have made new progress in the treatment of cancer.Phototherapy is a non-invasive treatment technology with many advantages such as remote controllability,improved selectivity and low system toxicity.Among them,photothermal therapy is a method of converting electromagnetic energy into local hyperthermia to cause cancer cell apoptosis which activated by near infrared(NIR)laser(650-900 nm)light absorption agent.The key to photothermal therapy is the selection of photothermal agents.So far,many inorganic nanomaterials have been widely studied for effective cancer treatment,but the clinical application of these drugs is still limited by some,such as complex synthetic processes and heavy metal ions Induced long-term toxicity.In contrast,small-molecule organic photothermal agents have many advantages over inorganic materials,such as inherently excellent biodegradability,low toxicity,and convenient synthetic pathways.Therefore,the development of organic photothermal agents is an important research direction for future anti-cancer treatments.Organic semiconductor small molecules IHIC and ITIC have strong absorption in the near infrared region(NIR),so we believe that these two semiconductor small molecules have good photothermal therapeutic potential.However,it is inherently toxic and insoluble in water.It is necessary to improve its biocompatibility and select an appropriate drug carrier.Based on the above,the thesis mainly did the following work:(1)We designed and synthesized a liposome loaded with semiconductor small molecule IHIC / ITIC based on dioleoylphosphatidylethanolamine(DOPE),and explored a series of characterization of its photothermal and photoacoustic properties both intracellular in mice.The liposome-loaded IHIC / ITIC can be evenly dispersed in water with a particle size of about 50 nm,which is well dispersed and has good stability.According to calculations,the encapsulation efficiency can reach 40.88%(IHIC)and 38.61%(ITIC).Cytotoxicity experiments confirmed that the synthesized products had good anti-tumor activity in vitro,and the photothermal conversion efficiency was 39.5%(IHIC)and 42.1%(ITIC),respectively.The product has strong signals in in vitro and in vivo photoacoustic imaging experiments,proving its potential for tumor imaging.In addition,it has achieved a good curative effect in photothermal therapy of living mice,which provides a certain reference significance for the study of small semiconductor molecules for photothermal / photoacoustic dual-mode therapy,which is beneficial to the future of small organic semiconductor molecules application of anti-cancer treatment.(2)In order to prevent the loss of the drug during the delivery process,we adopted a new idea,selected a GSH-responsive hollow mesoporous manganese dioxide microsphere as the drug carrier,and performed a series of performances on the carrier the study.Hollow mesoporous manganese dioxide nanospheres with a particle size below 100 nm were prepared by hydrothermal method,and an in vitro response experiment was conducted to simulate the tumor microenvironment.Experiments show that hollow mesoporous manganese dioxide nanospheres can be degraded at low p H and glutathione peptide response thus can be used to deliver drugs or photothermal agents,and perform coordinated cancer imaging and treatment.