發(fā)布時間：2018-03-27 12:26

  本文選題：光熱治療　切入點：光熱轉(zhuǎn)換試劑　出處：《東華大學》2016年博士論文

【摘要】：光熱治療技術是近年來新興發(fā)展的一種腫瘤治療方法,其工作原理是:利用對生物組織有較好通透性的近紅外光(NIR)照射光熱轉(zhuǎn)換試劑,在局部位置生成“高熱”并誘導癌細胞死亡、腫瘤壞死。該技術因具有簡便、可控、副作用小等特點而備受青睞。光熱轉(zhuǎn)換試劑是光熱治療技術革新的關鍵。隨著納米科技的不斷發(fā)展,納米材料在光熱治療研究中取得了越來越廣泛的應用。一些具有NIR響應的納米材料和功能復合物被陸續(xù)報道并用于光熱治療和聯(lián)合治療腫瘤當中。本論文首先簡要介紹光熱治療技術,并對光熱轉(zhuǎn)換試劑可能存在的光吸收機制進行了小結,然后對近幾年來光熱轉(zhuǎn)換試劑取得的重要進展進行評論,以期為開發(fā)更加低毒、高效、功能多樣的光熱轉(zhuǎn)換試劑提供有益參考。在此基礎上,就光熱轉(zhuǎn)換試劑存在的某些問題,如光熱轉(zhuǎn)換效率低、合成復雜且毒性大、功能單一,開展了以下幾方面的具體工作:(1)親水性、高光熱轉(zhuǎn)換效率的Bi_2S_3納米花的調(diào)控合成及熱消融癌細胞應用目前報道的鉍基材料光熱轉(zhuǎn)換效率較低。本論文利用一步溶劑熱法分別制備了親水性的Bi_2S_3納米花和Bi_2S_3納米帶。研究發(fā)現(xiàn),反應中加入合適量的聚乙烯吡咯烷酮(PVP)后,不但導致Bi_2S_3納米材料的形貌從納米帶狀轉(zhuǎn)變成尺寸均勻的納米花,而且還對其膠體分散性、結晶度以及NIR吸收都有很大改變。在相同實驗條件下的808 nm激光器照射下,Bi_2S_3納米花的光熱轉(zhuǎn)換效率高達64.3%,幾乎是Bi_2S_3納米帶(ηT=36.5%)的兩倍,比金納米棒也要高(ηT=54.3%)。將Bi_2S_3納米花用于808 nm激光驅(qū)動的光熱治療中,在體內(nèi)外都能夠快速誘導癌細胞死亡。Bi_2S_3納米花高效的光熱轉(zhuǎn)換效率可以歸功于以下三個方面:首先,Bi_2S_3納米花在激發(fā)波長(808 nm)處具有很強的吸收,其質(zhì)量吸收系數(shù)達20.5L?g~(-1)?cm~(-1);其次,Bi_2S_3納米花的三維超結構和大比表面,增強了光電子在材料表面的反射、折射、吸收等作用,延長了其與材料相互作用的時間,進一步提高了材料對光電子的利用率;最后,Bi_2S_3納米花具有更窄的能量帶隙(Eg=0.79 e V),可以提高材料對低能量光的利用率。這些有效提高光熱轉(zhuǎn)換效率的策略,將為開發(fā)具有高光熱轉(zhuǎn)換效率的新型光熱轉(zhuǎn)換試劑提供有益的借鑒。(2)水合氧化釕光熱轉(zhuǎn)換試劑的開發(fā)及其光熱治療腫瘤應用基于綠色環(huán)保合成納米材料的考慮,利用一步水熱法,通過RuCl_3?xH_2O在水相中水解制備了具有較好NIR吸收的水合氧化釕(RuO_2?xH_2O)納米粒子。RuO_2?xH_2O納米粒子的近紅外光吸收可能與RuO_2晶體對水或質(zhì)子的吸附/脫附作用有關。因為H2O或H+的吸/脫附作用可以使Ru元素的化學環(huán)境發(fā)生改變,導致Ru在多種價態(tài)電子對中發(fā)生電子躍遷,從而使RuO_2?xH_2O納米材料在水溶液中擁有較強的近紅外光吸收。PVP改性后的RuO_2?xH_2O納米材料(PVP-RuO_2)在生理介質(zhì)中有良好的分散性及生物相容性,其在808 nm激光誘導下的光熱轉(zhuǎn)換效率為54.8%,在體內(nèi)外都可以快速升溫并殺死癌細胞,并完全抑制腫瘤生長。因此,水合氧化釕可以作為一類新型的潛在光熱轉(zhuǎn)換試劑用于癌癥的熱療。(3)核殼結構的FeWO_4@PPy納米復合材料的制備及在腫瘤診療中的應用成像診斷可以指導癌癥的治療。根據(jù)報道,聚吡咯(PPy)是一種生物相容性好的可降解有機光熱轉(zhuǎn)換試劑,但性能簡單;FeWO_4是一種潛在的MRI/CT雙模造影成像劑,但光熱轉(zhuǎn)換性能差。將這兩種廉價易得的材料復合構成具有成像診斷和光熱治療的多功能納米復合物,在診療癌癥方面具有潛在應用價值。本論文首先用水熱法合成了FeWO_4納米材料,再用原位聚合的方法在其表面包覆了一層聚吡咯,制備了一種無機/有機雜化的核殼結構的FeWO_4@PPy納米復合材料。FeWO_4@PPy納米復合材料在溶液中獲得了較好的MRI/CT雙模成像造影效果,其橫向弛豫率r2為1.46 m M~(-1)?s~(-1),對X射線衰減系數(shù)為12.99HU?m M~(-1),而后者比碘海醇的衰減系數(shù)還高(5.74 HU?m M~(-1))。因此,將FeWO_4@PPy納米復合材料注射到荷瘤鼠后,實現(xiàn)了對He La腫瘤的MRI/CT成像信號的增敏作用,提高了腫瘤的辨識度。血液循環(huán)代謝和組織分布研究表明,靜脈注射的FeWO_4@PPy納米復合材料,4小時內(nèi)可以完全從血液中清除,在網(wǎng)狀內(nèi)皮系統(tǒng)有很高的富集,如肝臟(67.2±1.8%ID/g)和脾臟(33.1±5.0%ID/g)。由于腫瘤特有的高通透及滯留(EPR)效應,納米復合材料在He La腫瘤中也有一定的富集率(1.2±0.4%ID/g)。在808 nm激光誘導下,該納米復合材料可以產(chǎn)生足夠高溫(光熱轉(zhuǎn)換效率為56.1%)并殺死癌細胞,完全抑制腫瘤生長。因此,FeWO_4@PPy納米復合材料在癌癥的多模成像診斷和光熱治療中展現(xiàn)了巨大的應用潛力。
[Abstract]:The light and heat treatment technology is a new method for the treatment of tumor development in recent years, its working principle is: the use of a good permeability near infrared (NIR) radiation on biological tissue photothermal conversion reagent, locally generated "high fever" and induce cancer cell death and tumor necrosis. The technology has a simple, controllable, side the role of small favored. Photothermal conversion reagent is the key innovation of photothermal therapy technology. With the development of nano technology, nano materials has been more and more widely used in photothermal therapy research. Some have NIR ring nano materials and functional composites should be reported and used in photothermal therapy and combined treatment of tumors. This paper first briefly introduces photothermal therapy technology, and the possible photothermal conversion reagent absorption mechanism were summarized, and in recent years the photothermal conversion kit Important progress of comments, in order to develop more efficient, low toxicity, provide a useful reference reagent photothermal conversion of functional diversity. On this basis, some problems exist on the photothermal conversion reagent, such as photothermal conversion efficiency is low, the synthesis of complex and high toxicity, single function, carry out the following works: (1) hydrophilic, high light heat conversion efficiency Bi_2S_3 nanoflower control synthesis and thermal ablation of bismuth based photothermal cancer cell applications currently reported lower conversion efficiency. This paper made hydrophilic Bi_2S_3 nanoflower and Bi_2S_3 nanobelts were prepared by one-step solvothermal method. The study found that adding appropriate amount of in the reaction of polyvinylpyrrolidone (PVP), which not only led to the morphology of Bi_2S_3 nano materials from nano ribbon into nano uniform size of flowers, but also on the dispersion of the colloid, crystallinity and NIR absorption are greatly Change. In the same experimental conditions 808 nm laser irradiation, the photothermal conversion efficiency of Bi_2S_3 nano flowers up to 64.3%, almost Bi_2S_3 nanoribbons (n T=36.5%) two times, also higher than the gold nanorods (T=54.3%). Bi_2S_3 nano flower for light heat treatment of 808 nm laser driver. Can rapid photothermal induced cancer cell death.Bi_2S_3 nanoflower high conversion efficiency can be attributed to the following three aspects: firstly, both in vitro and in vivo Bi_2S_3 nanoflower at excitation wavelength (808 nm) with strong absorption, the absorption coefficient of 20.5L? G ~ (-1) cm~ (-1); second? Bi_2S_3, nano flowers three-dimensional super structure and high surface area, enhanced photoemission in material surface reflection, refraction, absorption, extend its interaction with material time, further improve the utilization rate of materials on the photoelectron; finally, Bi_2S_3 nanoflowers have narrower The energy band gap (Eg=0.79 e V), can improve the material utilization of the low energy light rate. These can effectively improve the thermal efficiency of the strategy, will develop new high light heat conversion efficiency of the solar thermal conversion kit provided useful reference. (2) the development of hydrated ruthenium oxide and photothermal photothermal conversion reagent used to treat tumor based on the green synthesis of nano materials, using a one-step hydrothermal method by RuCl_3? XH_2O in aqueous solution was prepared by hydrolysis with hydrated ruthenium oxide better absorption of NIR (RuO_2? XH_2O).RuO_2 nanoparticles? Near infrared absorption of xH_2O nanoparticles and RuO_2 crystal of water or proton adsorption / desorption effect because H2O or H+ adsorption / desorption effect can make the chemical environment of Ru elements changed, resulting in a variety of Ru valence electron pair in the electronic transition, so that the RuO_2? XH_2O nanoparticles in aqueous solution. A near infrared absorption.PVP modified RuO_2 strong? XH_2O nano materials (PVP-RuO_2) in physiological medium dispersion and good biological compatibility, the 808 nm laser induced photothermal conversion efficiency of 54.8%, both in vivo and in vitro can quickly heat up and kill cancer cells, and inhibit the tumor completely growth. Therefore, hydrous ruthenium oxide can be used as a new type of potential photothermal conversion reagent for the treatment of cancer. (3) FeWO_4@PPy nanocomposites with core-shell structure of the preparation and application of imaging in diagnosis and treatment of cancer diagnosis can guide the treatment of cancer. According to reports, polypyrrole (PPy) is a biocompatible good degradable organic photothermal conversion reagent, but the performance is simple; FeWO_4 is a potential MRI/CT dual-mode imaging agent, but the conversion of poor performance. The two kinds of cheap materials constitute the imaging diagnosis and light Multifunctional nano composite heat treatment, has the potential application value in the diagnosis and treatment of cancer. This paper first hydrothermal method FeWO_4 nanomaterials were synthesized by in situ polymerization method, coated with a layer of polypyrrole on the surface, the preparation of a novel inorganic / organic hybrid core-shell FeWO_4@PPy nanocomposite.FeWO_4@PPy nano composite the material has a better MRI/CT dual-mode imaging contrast effect in solution, the transverse relaxation rate of R2 was 1.46 m M~ (-1)? S~ (-1), X ray attenuation coefficient is 12.99HU? M M~ (-1), and the latter is higher than the attenuation coefficient of iohexol (5.74 HU? M M~ (-1)). Therefore, the injection of FeWO_4@PPy nano composite materials to tumor bearing mice after the sensitization of MRI/CT imaging signal on He La tumor, improve the tumor identification. The blood circulation metabolism and tissue distribution studies showed that intravenous injection of FeWO_4@PPy nano complex The material, within 4 hours can be completely removed from the blood, in the reticuloendothelial system has very high enrichment, such as liver (67.2 + 1.8%ID/g) and spleen (33.1 + 5.0%ID/g). The tumor specific high permeability and retention (EPR) effect, nano composite materials have a certain accumulation rate in He La tumors (1.2 + 0.4%ID/g). In the 808 nm laser induced by the nano composite material can produce enough high temperature (photothermal conversion efficiency of 56.1%) and kill cancer cells, completely inhibited tumor growth. Therefore, FeWO_4@PPy nanocomposites show great potential applications in the diagnosis and treatment of cancer in multimode photothermal imaging.

【學位授予單位】：東華大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R730.5

【參考文獻】

相關期刊論文 前1條

1 Guosheng Song;Linbo Han;Weiwei Zou;Zhiyin Xiao;Xiao Juan Huang;Zongyi Qin;Rujia Zou;Junqing Hu;;A Novel Photothermal Nanocrystals of Cu_7S_4 Hollow Structure for Efficient Ablation of Cancer Cells[J];Nano-Micro Letters;2014年02期

，

本文編號：1671520