本文選題：金屬卟啉衍生物　切入點(diǎn)：金屬酞菁衍生物　出處：《太原理工大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：癌癥是全球范圍內(nèi)威脅人類健康的一大殺手,它和心血管疾病已經(jīng)成為醫(yī)學(xué)上難以克服的兩大難題,因此癌癥的診斷和治療成為材料學(xué)、化學(xué)和生物醫(yī)學(xué)等領(lǐng)域的研究熱點(diǎn)之一。癌癥的診斷技術(shù)包括各種非入侵式的腫瘤成像技術(shù),例如核磁共振成像、超聲波成像、熒光成像等,通過這些方法可診斷腫瘤組織的形態(tài)及代謝情況。其中,熒光成像技術(shù)靈敏度高,副作用小,不含放射性物質(zhì)且操作簡單,因此安全性更好。就治療技術(shù)而言,光動(dòng)力治療(PDT)是一種新興的腫瘤治療手段,它具有腫瘤靶向性好,副作用小,不損傷病人正常器官等特點(diǎn),因而近些年來PDT發(fā)展迅速。光動(dòng)力治療需具備三個(gè)基本要素:光敏劑、激發(fā)光與分子氧。卟啉衍生物是一類傳統(tǒng)的光敏劑,已經(jīng)被很多國家批準(zhǔn)應(yīng)用于臨床實(shí)踐中。其中鉑卟啉和鈀卟啉的衍生物具有磷光量子產(chǎn)率高、三線態(tài)壽命長、斯托克斯位移大、光穩(wěn)定性好等優(yōu)點(diǎn),因此其作為磷光探針在熒光成像上有很高的研究價(jià)值。酞菁作為光動(dòng)力治療的第二類光敏劑有其獨(dú)特優(yōu)勢:化學(xué)性質(zhì)穩(wěn)定,合成方法簡單,在可見光區(qū)600—700 nm的摩爾吸光系數(shù)是卟啉的20-50倍,無毒,對腫瘤組織具有選擇性和較強(qiáng)殺傷力,且對周圍正常組織影響較小,因此適用于癌癥光動(dòng)力學(xué)治療。但是文獻(xiàn)報(bào)道的大多數(shù)卟啉衍生物和酞菁配合物在水中溶解度較低,并且目前臨床應(yīng)用的光敏劑存在組織選擇性差和聚集誘導(dǎo)猝滅等問題,在很大程度上限制了其在生物醫(yī)學(xué)領(lǐng)域的應(yīng)用。因此我們致力于合成多個(gè)系列基于金屬卟啉和酞菁的的診療一體化高水溶性熒光納米探針,并探究其在癌細(xì)胞診療方面的應(yīng)用。本論文的主要研究內(nèi)容如下:1.設(shè)計(jì)合成了金屬卟啉小分子(PtTPP和PdTPP)和金屬卟啉聚合物(Pt-P和Pd-P);將PtTPP,PdTPP,Pt-P,Pd-P通過再沉淀法制備成納米顆粒(NPs);利用核磁共振(NMR)、紅外分光光度計(jì)(FT-IR)、動(dòng)態(tài)光散射粒度儀(DLS)、紫外可見吸收分光光度計(jì)(UV-vis)、熒光分光光度計(jì)(PL)等對化合物的結(jié)構(gòu)、尺寸與性能進(jìn)行測試表征;激光掃描共聚焦熒光顯微鏡成像實(shí)驗(yàn)結(jié)果表明Pt-PNPs對HeLa細(xì)胞具有良好的標(biāo)記功能,而且Pt-PNPs隨著氧濃度的降低熒光壽命有所延長;但是這些納米顆粒均在細(xì)胞外發(fā)生不同程度的團(tuán)聚,影響細(xì)胞成像質(zhì)量,從而有必要進(jìn)一步提高金屬卟啉聚合物納米顆粒的水溶性,增大其生物相容性。2.利用b-環(huán)糊精(b-CD)對金屬卟啉化合物進(jìn)行修飾合成了PtTCPP@b-CD和PdTCPP@b-CD,成功改善了金屬卟啉類化合物的水溶性,之后利用CTAB對PtTCPP@b-CD和PdTCPP@b-CD進(jìn)行表面電位改性,從Zeta電位測試結(jié)果得知表面電荷由負(fù)性轉(zhuǎn)變?yōu)檎�。同樣利�?H NMR、FT-IR、DLS、UV-vis、PL等測試方法對化合物的結(jié)構(gòu)與性能進(jìn)行詳細(xì)測試表征;MTT實(shí)驗(yàn)結(jié)果表明PtTCPP@b-CD@CTAB和PdTCPP@b-CD@CTAB納米探針生物毒性較小;激光掃描共聚焦熒光顯微鏡成像實(shí)驗(yàn)結(jié)果表明這些納米探針對癌細(xì)胞具有靶向性識別作用,同時(shí)還有高濃度熒光發(fā)射增強(qiáng)性質(zhì),這些研究結(jié)果證明了PtTCPP@b-CD@CTAB和PdTCPP@b-CD@CTAB納米探針具有癌細(xì)胞診斷應(yīng)用的潛力。3.利用b-CD修飾金屬酞菁合成了PtTCPc@b-CD和PdTCPc@b-CD,大大提高了金屬酞菁化合物的水溶性,同樣利用CTAB對PtTCPc@b-CD和PdTCPc@b-CD進(jìn)行表面電位改性(由負(fù)性轉(zhuǎn)為正性)。利用1H NMR、FT-IR、DLS、UV-vis、PL等對化合物的結(jié)構(gòu)與性能進(jìn)行詳細(xì)測試表征;MTT實(shí)驗(yàn)結(jié)果表明PtTCPc@b-CD@CTAB和PdTCPc@b-CD@CTAB生物毒性較小;激光掃描共聚焦熒光顯微鏡成像實(shí)驗(yàn)表明PdTCPc@b-CD@CTAB納米探針具有良好的近紅外細(xì)胞成像功能。
[Abstract]:Cancer is a major killer worldwide threat to human health and cardiovascular disease, it has become the two largest medical problem difficult to overcome, so the diagnosis and treatment of cancer has become one of the research hotspot in materials science, chemistry and biomedical fields. Diagnosis of cancer including tumor non invasive imaging techniques, such as magnetic resonance imaging, ultrasonic imaging, fluorescence imaging, diagnosis of morphology and metabolism of tumor tissue by these methods. The fluorescence imaging technique with high sensitivity, small side effect, non radioactive material and has the advantages of simple operation, better safety. Therefore treatment technology, photodynamic therapy (PDT) is a new tumor the treatment means, it has tumor targeting, small side effect, no damage to patients with normal organs and other characteristics, so in recent years the rapid development of PDT. Photodynamic therapy requires three base The elements: photosensitizer, luminescence and molecular oxygen. The porphyrin derivative is a kind of traditional photosensitizer, has been approved by many countries used in clinical practice. The platinum and palladium porphyrin porphyrin derivatives with high phosphorescence quantum yield of three line state, long service life, large Stokes shift, has the advantages of good light stability, so as to the phosphorescence probes in fluorescence imaging has high research value. Second kind of photosensitizer phthalocyanine as photodynamic therapy has its unique advantages: chemical stability, simple synthetic method, in 600 - 700 nm Moore visible light absorption coefficient is 20-50 times, porphyrin non-toxic, selectivity and strong lethality of tumor tissue, and less impact on the surrounding normal tissue, so it is suitable for photodynamic therapy of cancer. But most of the porphyrin derivatives and phthalocyanine complexes reported low solubility in water, and now The clinical application of the photosensitizer problems of poor tissue selectivity and aggregation induced quenching, which limits its application in the biomedical field to a great extent. Therefore, we are committed to the synthesis of multiple series of metal porphyrin and phthalocyanine and the integration of highly water-soluble fluorescent probes based on, and explore its application in the diagnosis of cancer cells. The research contents of this thesis are as follows: 1. the synthesis of metal porphyrin molecules (PtTPP and PdTPP) and the design of metal porphyrin polymers (Pt-P and Pd-P); PtTPP, PdTPP, Pt-P, Pd-P were prepared by reprecipitation method into nanoparticles (NPs); the use of nuclear magnetic resonance (NMR), infrared spectrophotometer (FT-IR), dynamic light scattering particle analyzer (DLS), UV VIS spectrophotometer (UV-vis), fluorescence spectrophotometer (PL) on the compound structure, size and performance were characterized; laser scanning confocal fluorescence microscope The experimental results show that Pt-PNPs has good markers of HeLa cells, and Pt-PNPs with the decrease of oxygen concentration and fluorescence increased life; but these nanoparticles are outside the cells of different degrees of aggregation, affecting cell imaging quality, so it is necessary to further improve the metal porphyrin polymer nanoparticles increases water solubility, biocompatibility.2. b- (b-CD) using cyclodextrin to metal porphyrin compounds were synthesized and modified PtTCPP@b-CD PdTCPP@b-CD, succeeded in improving the metalloporphyrin solubility in water, after the use of CTAB surface potential on PtTCPP@b-CD and PdTCPP@b-CD modified Zeta potential, from the test results that the surface charge changed from negative to positive. By utilizing the same 1H NMR, FT-IR, DLS, UV-vis, structure and properties of PL test method for the characterization of compounds with MTT; the experimental results show that PtTCPP@b-CD @CTAB and PdTCPP@b-CD@CTAB nano probe biological toxicity is small; laser scanning confocal fluorescence microscopy imaging experimental results show that the nano probe has a role to recognition of cancer cells, as well as high concentration enhanced fluorescence emission properties, these results show that PtTCPP@b-CD@CTAB and PdTCPP@b-CD@CTAB nano probe has the potential application of.3. diagnosis of cancer cells by using b-CD modified metal phthalocyanine PtTCPc@b-CD and PdTCPc@b-CD were synthesized, greatly improves the water solubility of metal phthalocyanine compounds, also use CTAB on PtTCPc@b-CD and PdTCPc@b-CD surface potential modification (from negative to positive). Using 1H NMR, FT-IR, DLS, UV-vis, PL etc. the structure and properties of these compounds were characterized with MTT; the experimental results show that PtTCPc@b-CD@CTAB and PdTCPc@b-CD@CTAB toxicity is small; laser scanning confocal fluorescence microscopy imaging experiment It is shown that the PdTCPc@b-CD@CTAB nanoprobe has a good imaging function of near infrared cells.

【學(xué)位授予單位】：太原理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R91;R96

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