本文選題：納米粒子 + 聚合物　； 參考：《吉林大學》2017年博士論文

【摘要】：惡性腫瘤也被稱為癌癥,具有治愈困難,易于轉移和復發(fā)的特點,再加上傳統(tǒng)手術、放射療法、化學療法等毒副作用,使得癌癥的致死率非常高,因而癌癥也被稱為威脅人類健康的第一殺手。避開傳統(tǒng)癌癥診療方法的弊端,將納米技術應用于癌癥的診療,發(fā)展新型診療方法學,成為癌癥治療的又一線曙光。我的工作圍繞著對超分子弱相互作用的理解,構筑具有腫瘤診療性能的納米復合試劑。在第二章中,我們以15-20nm的球形金納米粒子作為構筑基元,通過偶極吸引誘導一維鏈狀組裝體的產生,組裝結構保持了金球的穩(wěn)定性,并增強了在近紅外光區(qū)的消光能力,在808nm處的消光系數隨著組裝體鏈長的增加而增強。為了進一步提高膠體穩(wěn)定性,我還在組裝體外包覆聚吡咯殼層,殼層的引入進一步增強了光熱轉化性能,并將復合物的光熱轉化效率提高到接近70%。體外的細胞實驗表明,復合材料在激光照射下能夠有效殺滅癌細胞,動物實驗結果表明金鏈復合物在808nm激光照射下能夠有效抑制腫瘤生長。為了防止治療后的腫瘤復發(fā),我們進一步將光熱治療與化療結合將銅離子配合物負載于殼聚糖中,制備成納米粒子。復合物納米粒子的腫瘤抑制能力來源于光熱治療和化療性能,其中光熱治療是通過調節(jié)銅離子周圍的配體場,從而改變銅離子配合物在近紅外光區(qū)的光熱轉化性能;化療來源于銅離子的毒性,通過殼聚糖在體內緩慢降解逐漸釋放銅離子達到化療效果。動物實驗數據表明單獨的化療腫瘤抑制率為93.1%,結合光熱治療后,熱化療能夠完全消除腫瘤,并且在后續(xù)兩個月的觀察中沒有出現腫瘤復發(fā)。為了進一步提高納米試劑的安全性,在第三章中,我們將銅離子和鐵離子通過配位作用摻雜在聚苯胺納米梭中,制備了磁共振成像腫瘤診斷和熱化療性能的多功能試劑。過渡金屬離子摻雜在四個方面對聚苯胺性能帶來了提升:1.改變聚苯胺共軛能級,增強近紅外光區(qū)消光;2.納米梭表面正電性,與癌細胞產生快速粘附,有利于腫瘤滯留;3.摻雜的銅離子在巰基小分子刺激下釋放,形成化療;4.銅離子和鐵離子3d軌道中存在不成對電子,可以增強納米梭在磁共振成像T1中的造影能力。所以將納米梭通過靜脈注射到小鼠體內,結果顯示靜脈注射的納米梭能夠清晰標記腫瘤區(qū)域和邊界,并且可以通過化療抑制腫瘤生長,單獨的化療腫瘤抑制率為46.2%,結合光熱治療后,一次熱化療即可將腫瘤完全消除,并且兩個月內未觀測到復發(fā)。在第四章中,我們進一步利用聚苯胺納米梭表面的正電性,對超分子弱相互作用于腫瘤攝取的關系進行研究。在體外,靜電吸引可以使納米梭快速粘附在細胞表面,特別是對Hela細胞。進一步在活體腫瘤模型中,靜電吸引主動增強腫瘤對納米梭的滯留,納米梭在腫瘤區(qū)域的富集程度取決于納米梭與癌細胞間靜電吸引強度。因而,靜電吸引較強的Hela腫瘤對納米梭的富集率高達8.1%ID/g,而靜電作用較弱的KB腫瘤只有3.2%ID/g;在同一只小鼠的雙瘤模型中,KB和Hela腫瘤的富集率分別為2.8和7.9%ID/g。我還對比了PEG和SDS修飾后的銅離子摻雜聚苯胺納米粒子,修飾后的納米粒子具有對免疫系統(tǒng)增強的隱身效應,有利于腫瘤吞噬,但基于EPR效應的被動靶向結果仍然較靜電吸引驅動的非特異性腫瘤主動靶向的效果差。另外,由于納米梭沒有通過表面修飾來增強對免疫系統(tǒng)的隱身效應,進入小鼠體后會在肝部大量富集,并快速代謝,保證納米梭在使用時的安全性。
[Abstract]:Malignant tumor, also known as cancer, has the characteristics of cure difficulties, easy transfer and recurrence, combined with traditional surgery, radiation therapy, chemical therapy and other toxic side effects, which make cancer fatal, so cancer is also known as the first killer of human health. Avoid the drawbacks of traditional cancer diagnosis and treatment methods, and apply nanotechnology to the application of nanotechnology. In the second chapter, in the second chapter, we use the spherical gold nanoscale as the building element to induce one dimension through the dipole attraction. The assembly structure keeps the stability of the gold ball and strengthens the extinction ability in the near infrared light area. The extinction coefficient at 808nm increases with the increase of the length of the assembly chain. In order to further improve the colloid stability, I also assemble the polypyrrole shell in vitro. The introduction of the shell further enhanced the light and heat transfer. Experimental results show that the composite material can effectively kill the cancer cells under the laser irradiation. The results of animal experiments show that the gold chain complex can effectively inhibit the tumor growth under the 808nm laser irradiation. We will further prevent the recurrence of the tumor after the treatment, and we will further improve the tumor growth. Photothermal therapy and chemotherapy combine copper ion complexes with chitosan to prepare nanoparticles. The tumor inhibition ability of the composite nanoparticles is derived from photothermal therapy and chemotherapeutic performance, in which photothermal treatment changes the photothermal transformation of copper ion complexes in the near infrared light region by regulating the ligand field around copper ions. Yes, chemotherapy was derived from the toxicity of copper ions and gradually released copper ions through the slow degradation of chitosan in the body to achieve the effect of chemotherapy. Animal experimental data showed that the tumor inhibition rate of a single chemotherapeutic tumor was 93.1%. After photothermal therapy, chemotherapy could completely eliminate the tumor, and no recurrence was found in the follow-up for the next two months. In order to further improve the safety of nanoscale, in the third chapter, we doped the copper and iron ions in the polyaniline nanossifon by coordination, and prepared the multi-functional reagents for the diagnosis of tumor and the performance of the thermo chemotherapy. The transition metal ions doped in four sides brought about the enhancement of polyaniline performance: 1. to change polyphenylene. Amines conjugated energy levels, enhance the extinction of near infrared light area; 2. nanoscale spindle surface positively charged with cancer cells, which is beneficial to the retention of cancer cells; 3. doped copper ions are released under the small molecule stimulation of sulfhydryl groups to form chemotherapy; 4. copper ions and iron ion 3D orbit are not paired electrons, which can enhance the fabrication of nanoscale in magnetic resonance imaging (MRI). Therefore, the nanossio was injected into the mice by intravenous injection. The results showed that the intravenous nanoscale could clearly mark the tumor area and boundary, and could inhibit the tumor growth by chemotherapy. The tumor inhibition rate of the individual chemotherapy was 46.2%. After photothermal therapy, the tumor could be completely eliminated by one heat chemotherapy, and two In the fourth chapter, in the fourth chapter, we further used the positive power of the polyaniline nanoscale surface to study the relationship between the supramolecular weak interaction in the tumor uptake. In vitro, the electrostatic attraction can make the nanossies adhere to the cell surface rapidly, especially on the Hela cells. The enrichment of nanossie in tumor area depends on the electrostatic attraction between nanossie and cancer cells. Therefore, the enrichment rate of the Hela tumor with strong electrostatic attraction is up to 8.1%ID/g, while the KB tumor with weak electrostatic action is only 3.2%ID/g; in the double tumor model of the same mouse, KB The enrichment rates of the Hela and Hela tumor were respectively 7.9%ID/g. and I also compared the copper ion doped polyaniline nanoparticles modified by PEG and SDS. The modified nanoparticles have the stealth effect on the immune system, which is beneficial to the tumor, but the passive target based on the EPR effect is still more than the non specific tumor driven by the electrostatic attraction. The effect of active targeting is poor. In addition, because the nanossibon has not been modified by surface modification to enhance the stealth effect on the immune system, after entering the mouse body, it will accumulate in the liver and metabolize quickly, so as to ensure the safety of the nanoscale in use.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：TQ421.7

【相似文獻】

相關期刊論文 前1條

1 陳石良,孫震,谷文英,陶文沂;灰樹花深層發(fā)酵菌絲體多糖的酶法提取及其抗腫瘤作用[J];無錫輕工大學學報;2000年04期

相關會議論文 前4條

1 白明東;郭紅云;張芳紅;唐清秀;張曉文;;甘肅隴南無花果對小鼠移植性腫瘤的抑制作用及微量元素含量測定[A];中國營養(yǎng)學會第八屆臨床營養(yǎng)學術會議暨第三屆營養(yǎng)與腫瘤會議論文摘要匯編[C];2001年

2 馬紅;左劍;蔡寧;郭箭;黃潔茹;陳愛青;梁e，

本文編號：2085603