發(fā)布時(shí)間：2018-06-24 12:41

  本文選題：納米診療劑 + 可降解聚合物納米粒子��； 參考：《華中科技大學(xué)》2016年博士論文

【摘要】：近年來(lái),納米技術(shù)在生物醫(yī)藥領(lǐng)域的快速發(fā)展為腫瘤診療一體化帶來(lái)了新機(jī)遇。新型納米診療劑具有高靈敏成像能力和靶向治療的特性,可實(shí)現(xiàn)癌癥診斷和治療效率最大化,并有效地克服傳統(tǒng)治療的毒副作用及耐藥性等棘手問(wèn)題。因此,設(shè)計(jì)和制備新型納米診療劑逐漸成為腫瘤有效治療的理想途徑之一。而在一系列新型納米診療劑中,多功能雜化納米材料由于結(jié)合了有機(jī)納米材料和無(wú)機(jī)納米材料各自的特性,具有設(shè)計(jì)性強(qiáng)、治療效率高和生物相容性好等顯著優(yōu)勢(shì),因此在腫瘤診療領(lǐng)域中具有良好的應(yīng)用前景。然而,如何設(shè)計(jì)和制備簡(jiǎn)單高效的多功能雜化納米載藥系統(tǒng)作為納米診療劑,仍然面臨著諸多挑戰(zhàn)。本論文分別設(shè)計(jì)和構(gòu)建了三種新型多功能聚合物雜化納米材料：尺寸均一、可控的可降解聚合物雜化納米粒子、脂質(zhì)體包覆的多功能金納米籠和聚合物/金納米粒子雜化組裝體,并研究了這些新型多功能雜化納米材料在腫瘤診療中的應(yīng)用,為新型納米診療劑的設(shè)計(jì)與制備提供了實(shí)驗(yàn)依據(jù)。本論文的主要研究?jī)?nèi)容如下：1.尺寸均一、可控的可降解聚合物雜化納米粒子的構(gòu)建及在腫瘤診療中的應(yīng)用。分別采用手動(dòng)膜擠出乳化法和自組織沉淀法成功地制備了尺寸均一的可降解聚合物納米粒子。通過(guò)改變實(shí)驗(yàn)參數(shù)對(duì)納米粒子的尺寸及其分布進(jìn)行了有效的調(diào)控。量子點(diǎn)、磁性納米粒子和抗腫瘤藥物等能同時(shí)包覆在聚合物納米粒子中,從而制備出多功能可降解雜化納米粒子,實(shí)現(xiàn)了熒光成像、磁共振成像、磁場(chǎng)誘導(dǎo)定向聚集以及抗腫瘤治療。負(fù)載抗腫瘤藥物的納米粒子具有較高的藥物包封率和負(fù)載量、優(yōu)良的藥物緩釋性能以及比裸藥更強(qiáng)的腫瘤細(xì)胞殺傷能力。另外,與乳化法制備的納米粒子相比,經(jīng)自組織沉淀法制備的無(wú)表面活性劑包覆的聚合物納米粒子具有更高的細(xì)胞吞噬率和更好的生物相容性。本研究提供了簡(jiǎn)單、快速地制備尺寸均一可降解聚合物載藥納米粒子的方法,為納米診療劑的制備提供了一定的實(shí)驗(yàn)依據(jù)。2.脂質(zhì)體包覆的多功能金納米籠的構(gòu)建及在腫瘤診療中的應(yīng)用。采用多元醇還原法和電流置換法制備了中空多孔的金納米籠。將脂質(zhì)體包覆在金納米籠的表面,不僅有效地增加了金納米籠的生物相容性、防止藥物泄露,還能將靶向樹(shù)突狀細(xì)胞的抗體通過(guò)化學(xué)鍵連接在脂質(zhì)體表面,或?qū)⒘字惷庖咦魟┣度胫|(zhì)體層中,有效地增強(qiáng)了免疫刺激響應(yīng)。還通過(guò)溶劑擴(kuò)散和真空干燥法有效地將免疫抗原多肽和近紅外光敏劑負(fù)載到金納米籠內(nèi)腔或脂質(zhì)體層中。這類多功能雜化金納米籠集藥物載體、熱療劑和熒光成像劑為一體,實(shí)現(xiàn)了熒光成像介導(dǎo)的光熱/免疫聯(lián)合治療或光熱/光動(dòng)力/免疫多重聯(lián)合治療,可望在腫瘤診療中發(fā)揮重要作用。3.聚合物/金納米粒子雜化組裝體的構(gòu)建及在腫瘤診療中的應(yīng)用。分別采用超分子誘導(dǎo)和二維受限自組裝的方法構(gòu)建了棒狀的聚合物/金納米粒子雜化組裝體。提出了通過(guò)改變金納米粒子表面化學(xué)性質(zhì)來(lái)準(zhǔn)確調(diào)控金納米粒子在棒狀聚合物膠束中分布的途徑；研究了金納米粒子的體積分?jǐn)?shù)、尺寸和超分子微區(qū)尺寸等因素對(duì)金納米粒子空間分布和雜化膠束形貌的影響。此外,基于聚合物修飾的金納米粒子在二維納米孔道中受限組裝,制備出了在本體中難以得到的、具有新穎有序結(jié)構(gòu)的棒狀雜化組裝體。受限效應(yīng)對(duì)金納米粒子的粒間距、組裝體的結(jié)構(gòu)及其光學(xué)性能起到了主要調(diào)節(jié)作用,使組裝體具有良好的細(xì)胞暗場(chǎng)成像能力和光熱轉(zhuǎn)換性能。本研究為功能性復(fù)合材料的設(shè)計(jì)和制備提供了實(shí)驗(yàn)依據(jù),在腫瘤診療劑的制備和應(yīng)用中有重要的潛在應(yīng)用價(jià)值。以上工作提供了三種多功能雜化納米載藥系統(tǒng)的制備方法,并初步研究了它們?cè)谀[瘤診療中的應(yīng)用,為高效納米診療劑的設(shè)計(jì)與制備提供了一定的實(shí)驗(yàn)依據(jù)和技術(shù)支撐。
[Abstract]:In recent years, the rapid development of nanotechnology in the field of biological medicine has brought new opportunities for the integration of tumor diagnosis and treatment. The new nano diagnostic and therapeutic agents have high sensitivity imaging ability and target treatment characteristics, can realize the cancer diagnosis and treatment efficiency maximization, and effectively overcome the traditional treatment and drug resistance and drug resistance and other thorny problems. The design and preparation of new nano diagnostic and therapeutic agents have gradually become one of the ideal approaches for effective treatment of tumors. In a series of new nano diagnostic and therapeutic agents, multi-functional hybrid nanomaterials have strong design, high therapeutic efficiency and good biocompatibility because of their respective characteristics of organic nanomaterials and inorganic nanomaterials. Therefore, how to design and prepare a simple and efficient multifunction hybrid nano drug delivery system is still facing many challenges. Three new multi-functional polymer hybrid nanomaterials are designed and constructed in this paper: the size homogenization and controllable biodegradability Polymer hybrid nanoparticles, multi-functional gold nanometers coated with liposomes and polymer / gold nanoparticles hybrid assembly, and the application of these new multifunctional hybrid nanomaterials in the diagnosis and treatment of tumor, which provide experimental basis for the design and preparation of new nano diagnostic and therapeutic agents. The main contents of this paper are as follows: 1. feet The construction of a homogeneous and controllable biodegradable polymer hybrid nanoparticle and its application in the diagnosis and treatment of tumor. The size homogeneous biodegradable polymer nanoparticles were successfully prepared by manual membrane extrusion emulsification and self organizing precipitation. The size and distribution of the nanoparticles were effectively adjusted by changing the experimental parameters. Control. Quantum dots, magnetic nanoparticles and antitumor drugs can be encapsulated in the polymer nanoparticles at the same time, thus preparing multi-functional and biodegradable hybrid nanoparticles, realizing fluorescence imaging, magnetic resonance imaging, magnetic field induced orientation aggregation and antitumor therapy. Nanoparticles with anti swelling drugs have high drug encapsulation efficiency. In addition, the polymer nanoparticles, prepared by the self-organized precipitation method, have higher cell phagocytosis rate and better biocompatibility compared with the nanoparticles prepared by the emulsification method. This study provides a simple study. The method of preparing the homogeneous biodegradable polymer carrier nanoparticles is quickly prepared, which provides a certain experimental basis for the preparation of multi-functional gold nanoscale coated with.2. liposome and its application in the diagnosis and treatment of the tumor. The plastids coated on the surface of the gold nanoscale not only effectively increase the biocompatibility of the gold nanoscale, prevent the drug leakage, but also connect the antibody against the dendritic cells to the liposome surface through the chemical bonds, or the phospholipid immune adjuvant is embedded in the liposome layer, effectively enhancing the response of the immune stimulation. The immune antigen peptides and near infrared photosensitizers are effectively loaded into the inner cavity of the gold nanoscale or the liposome layer by the vacuum drying method. This kind of multifunctional hybrid gold nanoscale integrates the drug carrier, the thermotherapy agent and the fluorescent imager as a whole, and realizes the combined treatment of photothermal / immuno immunization mediated by fluorescence imaging, or the multiple combined treatment of photothermal / photodynamic / immunity. Therapy, which is expected to play an important role in the diagnosis and treatment of tumor, the construction of.3. polymer / gold nanoparticle hybrid assembly and its application in the diagnosis and treatment of tumor. The polymer / gold nanoparticle hybrid assembly has been constructed by using supramolecular induction and two-dimensional limited self assembly. The chemical properties of gold nanoparticles are proposed by changing the surface chemistry of gold nanoparticles. The distribution of gold nanoparticles in rod polymer micelles is accurately regulated and the influence of the volume fraction of gold nanoparticles, size and size of supramolecular microsphere on the spatial distribution of gold nanoparticles and the morphology of hybrid micelles are studied. In addition, the limited group of gold nanoparticles based on polymer modification in the two-dimensional nanopore channel. It has prepared a rod like hybrid assembly with novel and ordered structure which is difficult to obtain in the body. The limited effect has the main regulating effect on the particle space of gold nanoparticles, the structure of the assembly and the optical properties of the assembly, which makes the assembly have good imaging ability and photothermal conversion performance. This study is functional complex. The design and preparation of the composite materials provide an experimental basis and have an important potential application value in the preparation and application of the tumor diagnosis and treatment agents. The above work provides the preparation methods of three kinds of multi-functional hybrid nano drug delivery systems, and preliminary studies their application in the diagnosis and treatment of tumor, and provides the design and preparation of the efficient nano diagnosis and treatment agents. Certain experimental basis and technical support.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：TB383.1;R943;R730.4
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本文編號(hào)：2061560