用于光動力治療劑的氨基硅烷修飾的磁性納米復合粒子載藥體系的研究
發(fā)布時間:2018-05-17 12:19
本文選題:納米粒子 + 氨基硅烷 ; 參考:《山西大學》2015年碩士論文
【摘要】:光動力療法(PDT)是一種癌癥治療的新方法,其原理是受可見光照射的光敏劑分子吸收能量后,將能量傳遞給細胞中的氧分子,產(chǎn)生單線態(tài)氧或其它活性氧物種,從而導致細胞凋亡或壞死。目前用于PDT療法的光敏劑多為脂溶性化合物,其水溶性較差,生物利用率較低且對正常細胞存在一定的細胞毒性。為此,本文系統(tǒng)地研究了氨基硅烷修飾的磁性納米復合粒子作為光動力治療劑的載藥體系,以期在保留光動力治療劑脂溶性的同時改善其水溶性。開展了以下工作:(1)合成了Fe3O4@SiO2納米粒子,并采用兩種氨基硅烷對其進行表面修飾,得到了具有一定的分散性和生物相容性的納米復合粒子:Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS。采用IR、XRD等檢測手段對所得的復合粒子進行結(jié)構表征,并測定了其Zeta電位。Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS兩種納米復合粒子的粒徑分別為11.94 nm和12.85 nm,相應的Zeta電位分別為31.7 mV和32.7 mV。(2)將兩種鉑二亞胺類配合物,配合物Ⅰ和配合物Ⅱ負載到納米復合粒子表面,得到了載藥納米粒子,通過紫外-可見吸光度法分別測定了納米復合粒子的載藥率。結(jié)果表明:Fe3O4@SiO2-APTES、Fe3O4@SiO2-AEAPS和(Fe3O4/TA)@SiO2對配合物Ⅰ的載藥率分別為:7.6%,7.4%,7.5%;對配合物Ⅱ的載藥率分別為8.4%,8.3%,8.5%。(3)通過瓊脂糖凝膠電泳技術研究了載藥納米粒子對DNA的損傷行為。研究發(fā)現(xiàn),表面帶正電荷的納米復合粒子Fe3O4@SiO2-APTES和Fe3O4@SiO2-AEAPS對DNA基本無損傷,而表面帶負電荷的納米復合粒子(Fe3O4/TA)@SiO2對DNA存在一定程度的損傷。上述三種納米復合粒子載藥后在光照條件下對DNA均存在一定損傷,且這種損傷程度與藥物濃度呈正相關。(4)通過MTT實驗探究了配合物以及載藥納米粒子對腫瘤細胞的細胞活性的影響。結(jié)果表明,光照條件下,配合物以及載藥納米粒子對細胞增殖均存在一定程度的抑制作用,且不同配合物對不同種類的腫瘤細胞的增殖抑制程度不同。就載藥納米粒子對細胞增殖的抑制程度而言,表面帶正電荷的納米復合粒子載藥后對細胞增殖的抑制程度明顯優(yōu)于表面帶負電荷的納米復合粒子。(5)以流式細胞術測定了配合物及部分載藥納米粒子對MCF-7細胞周期的影響。結(jié)果表明,配合物及載藥納米粒子均對細胞周期不同階段產(chǎn)生一定的阻滯作用,進而影響細胞的增殖。
[Abstract]:Photodynamic therapy (PDT) is a new method of cancer treatment. The principle is that molecules of Guang Min, irradiated by visible light, absorb energy and transfer it to oxygen molecules in cells to produce singlet oxygen or other reactive oxygen species. This leads to apoptosis or necrosis. At present, most of the Guang Min agents used in PDT therapy are liposoluble compounds, which have poor water solubility, low bioavailability and cytotoxicity to normal cells. In order to improve the water-solubility of the photodynamic therapy agent, the magnetic nanoparticles modified with aminosilane were studied systematically as the drug delivery system of the photodynamic therapy agent in order to preserve the liposolubility of the photodynamic therapy agent at the same time. Fe3O4@SiO2 nanoparticles were synthesized and modified by two kinds of aminosilane. The nano-composite particles: Fe3O4SiO2-APTES and Fe3O4SiO2-AEAPSs with certain dispersity and biocompatibility were obtained. The structure of the composite particles was characterized by IR XRD. The Zeta potential, Fe _ 3O _ 4r Sio _ 2-APTES and Fe3O4@SiO2-AEAPS nanoparticles were determined to be 11.94 nm and 12.85 nm, respectively, and the corresponding Zeta potentials were 31.7 MV and 32.7 mV.-2 respectively. The two kinds of platinum diimide complexes, complexes 鈪,
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