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Construction Of Bionic Oxygen Nano-System And Evaluation Of The Characteristics Of Chemotherapeutics In Treating Tumors

Posted on:2022-10-18Degree:MasterType:Thesis
Country:ChinaCandidate:Z H ChenFull Text:PDF
GTID:2491306554960519Subject:Pharmacy
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To overcome the challenges of systemic toxicity and weak tumor selectivity caused by traditional antitumor drugs,numerous nanocarrier systems have been developed in recent decades,and their therapeutic effect has been improved to varying degrees.However,since tumor recurrence involves drug resistance and metastasis,single chemotherapy no longer meets diverse treatment requirements.Recently,the oxygen supply nanosystem has been proven to improve the therapeutic effect in many ways.Using this concept to combine chemotherapy-thermotherapy as the mainstay with oxygen supply as a supplementary method may become a new strategy for cancer treatment.In this work,by utilizing the unique properties of erythrocytes,an oxygen-rich bionic nano-drug delivery system was constructed as a novel nanocarrier system for simultaneous use of chemotherapy and photothermatic therapy.It is expected that it will be used in cancer.This subject has optimized the preparation method of the system from multiple angles and the EE%and LE%of DOX in the DPPR NPs prepared using the optimal parameters were 71.38%and 6.82%,respectively and the particle size is about170.3nm.There is a negative potential,and the potential value reaches-14.32mV at pH7.It is observed under the transmission electron microscope that its core is a bright white spherical structure surrounded by a complete dark gray cladding.The carrier was analyzed by dissolved oxygen,infrared scanning,and cell membrane protein analysis and all signs indicate that the vector is successfully constructed.The oxygen content of the nanocarrier was about 8.44mg/L.The infrared result showed the characteristic peak of PDA,The gel electrophoresis results also showed that the nanocarrier was successfully biomimetic.In addition,the carrier performed well in the photothermal conversion experiment.Because PDA has good photothermal conversion ability,the system temperature can be increased under the stimulation of near infrared(NIR)1.0W/cm~2 and 1.5W/cm~2 infrared light sources.15°C or 34.3°C.The stability results show that when stored in a liquid form at 4°C,its particle size,light-to-heat conversion performance,and oxygen loading have not changed significantly within 30 days,indicating that the stability of the drug loading system was well in all aspects.In vitro drug release data show that the release behavior of DOX in DPPR NPs has p H-dependent and near-infrared triggering characteristics.The folate modification of the red blood cell membrane effectively promotes the uptake of DPPR NPs by Hela cells.In the in vitro activity experiment,the level of reactive oxygen species in the cell is significantly increased.The use of infrared light can help it escape from the lysosome,which greatly increases the content of the drug in the cytoplasm thereby significantly inhibiting the growth of tumor cells and promoting the cell apoptosis and limits the recovery ability.Data from in vivo pharmacokinetics and biodistribution confirmed that DPPR NPs extended the half-life of DOX from 2.034h to 24.643h,and significantly reduce the concentration of DOX in the heart,thereby avoiding drug-related cardiotoxicity.More importantly,DPPR NPS has good targeting of cancer cells,so that the H22 tumor has good in vivo antitumor activity,and is highly safe.The tissue sections show that after DPPR NPS treatment,the main organs did not appear pathological damage,and the tumor tissue visible obvious cancer cell thermal ablation and nucleolar dissolution phenomenon.In the same manner,in the mouse also exhibited a good photothermal heating effect,within three minutes,mice can be raised to 44.5°C to 44.3°C,in terms of ultrasound imaging,due to DPPR NPS High concentration oxygen makes its contrast efficiency by 49.5%.In summary,the superior nature of red blood cells is used to construct a tumor-targeted bionic nanometric vector for chemotherapeutic drugs and photothermal drugs,and a synergistic effect is formed,which is considered to be an effective method for treating cancer.
Keywords/Search Tags:Chemical-photothermal therapy, Photodynamic therapy, DOX, PFOB, Ultrasound imaging
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