淡江大學覺生紀念圖書館 (TKU Library)
進階搜尋


系統識別號 U0002-1109201309105400
中文論文名稱 由幾丁聚醣/奈米金桿複合材料製備光控制藥物釋放奈米載體
英文論文名稱 Preparation of optically controlled drug-release nanocarriers made of chitosan/GNR composites
校院名稱 淡江大學
系所名稱(中) 化學工程與材料工程學系碩士班
系所名稱(英) Department of Chemical and Materials Engineering
學年度 101
學期 2
出版年 102
研究生中文姓名 鄭昕宜
研究生英文姓名 Shin-Yi Cheng
學號 600400377
學位類別 碩士
語文別 中文
口試日期 2013-07-23
論文頁數 131頁
口試委員 指導教授-董崇民
委員-邱文英
委員-蔡敏郎
中文關鍵字 溫度敏感型  酸鹼敏感型  可逆加成-斷裂鏈轉移聚合  奈米金桿  幾丁聚醣  藥物釋放系統 
英文關鍵字 thermal-responsive  pH-responsive  reversible addition-fragmentation chain transfer polymerization  gold nanorod  chitosan  drug delivery system 
學科別分類
中文摘要 本研究主要在製備具溫度及pH值雙重敏感性且光可調控的奈米複合載體以作為藥物控制釋放載體,利用近紅外光照射藥物載體,希望藉由奈米金桿光熱轉換的效應使其溫度上升,載體收縮而釋放藥物。此研究是利用丙烯酸(Acrylic acid, AA)與氮-異丙基丙烯醯胺 (N-isopropylamide, NIPAAm)以可逆加成-斷裂鏈轉移聚合(Reversible addition- fragmentation chain transfer polymerization,RAFT)活性自由基聚合方法合成末端帶有酸基和十二烷基三硫代碳酸酯的窄分子量分佈HOOC-PAA-b-PNIPAAm-CTA共聚物,作為環境敏感型高分子主體,並藉由調整高分子的pH值來控制低臨界溫度值(Lower critical solution temperature,LCST),當pH值調整至5.6以上,可以得到LCST接近於人體溫度37 oC。接著利用硼氫化鈉(NaBH4)將末端的三硫代碳酸酯基還原成巰基(-SH),發現水解後巰基含量提升至23.15 μmol/g,轉化率為57.2 %,隨後透過動態光散射及TEM證明高分子具自組裝的能力。接著將環境敏感型高分子於奈米金桿溶液中進行接枝反應以形成HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR複
合材料,其中奈米金桿是利用種晶生成法合成的,長寬分別為35.50(±3.7) nm和8.20(±1.7) nm,長寬比值(aspect rato , AR)為4.30(± 0.9)且形狀均一之奈米金桿(GNR),其表面電漿共振頻率(SPL,max)約在798 nm的近紅外光。實驗發現50 mg高分子與2.07×10-10 M的GNR反應24 h後具良好的穩定性,以動態光散射測量複合材料的 LCST約為37 oC,表示高分子在接枝上GNR後,對LCST值並無影響。最後將HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR溶液加入幾丁聚醣溶液中進行反應形成Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體,動態光散射及TEM探討其微胞型態,並以近紅外光(1000 mW)照射10分鐘後,由於奈米金桿的表面電漿共振效應,溫度可從25 oC上昇至40 oC,將可作為藥物釋放光熱轉換的能量來源,進行藥物釋放。
英文摘要 In this study﹐dual thermo- and pH-responsive and optical-controlled nanocomposites were prepared to serve as potential carriers for controlled delivery of drugs. After exposed to near-infrared (NIR) irradiation, the opto-thermal conversion characteristics of the gold nanorods (GNRs) in the nanocomposites allowed the transformation of light into heat, which triggered shrinkage of the carriers to release drugs. Reversible addition-fragmentation chain transfer (RAFT) polymerization of acrylic acid (AA) and N-isopropylamide (NIPAAm) was used to synthesize HOOC-PAA-b-PNIPAAm-CTA copolymers with acid and dodecyltrithiocarbonate end groups. The HOOC-PAA-b-PNIPAAm-CTA copolymers were environment-responsive and had narrow molecular weight distribution. Adjusting the pH to above 5.6 could bring the lower critical solution temperature (LCST) of the copolymers to around average normal body temperature (37 oC). NaBH4 was then used to reduce the trithiocarbonate group of the copolymers into thiol (-SH) group. After hydrolysis the content of sulphydryl group in the copolymers increased to 23.15 μmol/g with a conversion rate of 57.2 %. Self-assembling properties of the copolymers were observed by dynamics light scattering (DLS) and transmission electron microscopy (TEM). Uniform size of GNRs with a dimension of 35.50(±3.7) nm in length and 8.20(±1.7) nm in width resulting in an aspect rato (AR) of 4.30(± 0.9) and Longitudinal Surface plasmon resonance (SPL,max) at 798 nm were synthesized by seed-mediate growth method. Afterwards the environment responsive copolymers were added to the GNR solution and grafting reaction to synthesize HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR composites. The HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR composites prepared by incubating the copolymers (50mg) with GNRs (2.07×10-10 M) for 24 hours were found to have superior stability. DLS analysis showed that the LCST of the composites at around 37 oC, indicating that the grafting process did not affect the LCST. At last the dual-responsive polymer/gold nanorod (DRP/GNR) composite carriers were prepared by adding the HOOC-PAA-b-PNIPAAm-CTA/GNR and HOOC-PAA-b-PNIPAAm-SH/GNR solution into chitosan solution. DLS and TEM were used to investigate the micelle morphology of the DRP/GNR composite carriers. After 10 minutes of 1000 mW NIR irradiation, the temperature of the DRP/GNR solution increased from 25 oC to 40 oC due to the surface plasmon resonance effect of the GNRs, which could work as the energy resource of opto-thermal conversion for the composite carriers to release drugs.
論文目次 中文摘要 I
Abstract III
目錄 V
圖目錄 X
表目錄 XVII
第一章 緒論 1
1.1 前言 1
1.2 研究動機與目的 2
第二章 文獻回顧與基礎理論 4
2.1 活性自由基聚合法(Living Radical Polymerization) 4
2.1.1起始轉移終止劑法(Initiator transfer agent terminator,Iniferter) 4
2.1.2氮氧穩定自由基聚合法(Nitroxide mediated polymerization,NMP) 6
2.1.3原子轉移自由基聚合法(Atomic transfer radical polymerization,ATRP) 7
2.1.4可逆加成-斷裂鏈轉移聚合法(Reversible addition- fragmentation chain transfer polymerization,RAFT) 8
2.2 環境敏感型高分子 11
2.2.1 溫度敏感型高分子 12
2.2.2 酸鹼敏感型高分子 15
2.3 幾丁聚醣簡介及其應用 19
2.4 奈米金桿 22
2.4.1 奈米金桿的製備及其穩定性 24
2.4.2 奈米金桿的光熱性質及其應用 27
第三章 實驗方法與步驟 33
3.1 實驗藥品 33
3.2 實驗儀器 38
3.3實驗步驟 42
3.3.1高分子合成 42
3.3.1.1 合成HOOC-PAA-CTA 高分子 42
3.3.1.2合成HOOC-PAA-b-PNIPAAm-CTA團聯共聚物 44
3.3.1.3 合成HOOC-PAA-b-PNIPAAm-SH 高分子 45
3.3.1.4 Chitosan / HOOC-PAA-b-PNIPAAm-CTA及Chitosan / HOOC-PAA-b-PNIPAAm-SH 複合顆粒 47
3.3.1.5 奈米金桿(GNR)的製備 48
3.3.1.6 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體的製備 49
3.3.2性質測定 50
3.3.2.1 高分子的結構分析 50
3.3.2.2 丙烯酸單體轉化率及HOOC-PAA-CTA均聚物分子量計算 51
3.3.2.3 HOOC-PAA-b-PNIPAAm-CTA團聯共聚物分子量計算 52
3.3.2.4 高分子相變化溫度(LCST)的量測 52
3.3.2.5粒徑分析 52
3.3.2.6. 奈米金桿及Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體吸收峰測定(紫外光-可見光光譜分析,UV-Visible spectrophotometry) 53
3.3.2.7 高分子自組裝及奈米金桿(GNR) 形態分析(穿透式電子顯微鏡分析,TEM ) 53
3.3.2.8 HOOC-PAA-b-PNIPAAm-CTA 酸基含量測定 54
3.3.2.9 HOOC-PAA-b-PNIPAAm-SH巰基數的測量(Ellman’s test) 54
3.3.3 幾丁聚醣的純化及性質測定 55
3.3.3.1 幾丁聚醣純化 55
3.3.3.2 幾丁聚醣去乙醯度測定(Degree of deacetylation,DDA) 55
3.3.3.3 幾丁聚醣分子量測定 56
3.3.4 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體對激發光源之光熱效應 59
3.3.5 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體藥物包覆及釋放研究 59
第四章 結果與討論 61
4.1合成HOOC-PAA-CTA 高分子 61
4.1.1 HOOC-PAA-CTA高分子分子量 61
4.1.2 HOOC-PAA-CTA高分子結構分析 62
4.2 合成HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物 68
4.2.1 HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物分子量 68
4.2.2 HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物的結構分析 70
4.2.3 HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物粒徑分析 75
4.2.4 HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物酸基含量測定 79
4.2.5 HOOC-PAA-b-PNIPAAm-CTA 團聯共聚物穿透式電子顯微鏡分析(TEM) 79
4.3 合成HOOC-PAA-b-PNIPAAm-SH 高分子 80
4.3.1 HOOC-PAA-b-PNIPAAm-SH高分子分子量及結構分析 80
4.3.2 HOOC-PAA-b-PNIPAAm-SH高分子巰基含量 82
4.3.3不同pH值對 HOOC-PAA-b-PNIPAAm-SH高分子相變化溫度(LCST)的影響 84
4.3.4 HOOC-PAA-b-PNIPAAm-SH高分子穿透式電子顯微鏡分析(TEM) 86
4.4 幾丁聚醣的性質測定 87
4.4.1幾丁聚醣去乙醯度 87
4.4.2幾丁聚醣分子量 89
4.5 Chitosan/HOOC-PAA-b-PNIPAAm-CTA及Chitosan/HOOC-PAA-b-PNIPAAm-SH複合顆粒 90
4.5.1 Chitosan/HOOC-PAA-b-PNIPAAm-CTA及Chitosan/ HOOC-PAA-b-PNIPAAm-SH複合顆粒的結構分析 90
4.5.2 Chitosan/HOOC-PAA-b-PNIPAAm-CTA及 Chitosan/HOOC-PAA-b-PNIPAAm-SH高分子穿透式電子顯微鏡分析(TEM) 95
4.6 奈米金桿(GNR)性質與型態 95
4.7 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體 99
4.7.1 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體穩定性測試 99
4.7.2 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體粒徑分析 108
4.7.3 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體對激發光源之光熱效應 115
4.7.4 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體穿透式電子顯微鏡分析(TEM) 116
4.8 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體藥物包覆及釋放研究 117
第五章 結論 122
第六章 建議 124

圖目錄
圖2-1起始轉移終止劑法(Iniferter)合成機制 5
圖2-2氮氧穩定自由基聚合法(NMP)合成機制 6
圖2-3原子轉移自由基聚合法(ATRP)合成機制 7
圖2-4鏈轉移劑結構圖 8
圖2-5鏈轉移劑結構示意圖 9
圖2-6可逆加成-斷裂鏈轉移聚合反應(RAFT)機制 10
圖2-7 溫度敏感型高分子載體製備及藥物釋放機制示意圖 13
圖2-8 幾丁聚醣-聚(丙烯酸-co-氮異丙基丙烯醯胺)奈米載體示意圖 14
圖2-9 聚(氮異丙基丙烯醯胺-co-丙基丙烯酸)雙重敏感型微脂粒示意圖及其藥物釋放曲線 15
圖2-10 不同器官的pH值 16
圖2-11 酸鹼敏感型高分子釋放機制示意圖 17
圖2-12 幾丁聚醣/聚丙烯酸奈米微球製備機制及絲肽釋放曲線 18
圖2-13 幾丁聚醣/聚丙烯酸中空載體合成及藥物釋放機制 19
圖2-14 幾丁聚醣/聚丙烯酸中空載體包覆阿黴素細胞毒性測試(左)及藥物釋放曲線(右) 19
圖2-15 幾丁聚醣(Chitosan)結構式 20
圖2-16 奈米金球及奈米金桿表面電漿共振示意圖 23
圖2-17 不同顆粒大小及長短軸比對應奈米金溶液的顏色及其TEM圖 23
圖2-18 奈米金桿成長機制示意圖 25
圖2-19 高分子與奈米金桿鍵結示意圖 26
圖2-20 (a)血液及(b)奈米金桿溶液之UV-Vis吸收光譜圖(左虛線區塊為奈米金球;右虛線區塊為奈米金桿之吸收峰) 27
圖2-21 CGNR-FA合成示意圖 28
圖2-22 幾丁聚醣/奈米金桿(CS-AuNR)多功能奈米載體示意圖 29
圖2-23 PEG-NRs合成示意圖及光熱治療實驗結果 30
圖2-24 製備以Pluronic為基體的奈米載體與將GNR載入奈米載體中形成奈米金桿複合載體示意圖 31
圖2-25 (a)(b)注射奈米載體24小時後及(c)(d)注射奈米載體24小時和48小時後,用近紅外線雷射(808 nm、4 W/cm2)照射一次,照射時間為4分鐘的腫瘤體積變化與腫瘤的影像 32
圖3-1 HOOC-PAA –CTA均聚物反應結構式 42
圖3-2 RAFT反應裝置圖 43
圖3-3合成HOOC-PAA-CTA高分子流程圖 43
圖3-4 HOOC-PAA-b-PNIPAAm-CTA團聯共聚物反應結構式 44
圖3-5 合成HOOC-PAA-b-PNIPAAm-CTA團聯共聚物流程圖 45
圖3-6 合成HOOC-PAA-b-PNIPAAm-SH高分子流程圖 46
圖3-7 以NaBH4還原(水解) HOOC-PAA-b-PNIPAAm-CTA為HOOC-PAA-b-PNIPAAm-SH之反應式 46
圖3-8 CS/HOOC-PAA-b-PNIPAAm-CTA及CS/HOOC-PAA-b-PNIPAAm-SH複合顆粒流程圖 47
圖3-9 製備奈米金桿(GNR)流程圖 48
圖3-10 製備Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合載體的流程圖 50
圖3-11 Ellman’s reagent 反應流程圖 54
圖3-12 Dual-Responsive Polymer/Gold Nanorod (DRP/GNR)複合材料之光熱轉換實驗裝置示意圖 59
圖4-1 (a) RAFT agent (DMP) (b)ACVA (c)HOOC-PAA-CTA紅外線吸收光譜圖 62
圖4-2 HOOC-PAA-CTA0.6(MW=810 Da)之1H-NMR光譜圖 64
圖4-3 HOOC-PAA-CTA1.0(MW=1130 Da)之1H-NMR光譜圖 65
圖4-4 HOOC-PAA-CTA2.0(MW=1730 Da)之1H-NMR光譜圖 65
圖4-5 HOOC-PAA-CTA4.0(MW=2830 Da)之1H-NMR光譜圖 66
圖4-6利用RAFT合成HOOC-PAA-CTA高分子,轉化率(X)對反應時間及
偽一階反應動力(Pseudo first-order kinetic)作圖 67
圖4-7 HOOC-PAA-b-PNIPAAm-CTA (MW=29200 Da)之1H-NMR光譜圖 69
圖4-8 (a) HOOC-PAA-CTA(b)PNIPAAm(AIBN)(c)HOOC-PAA-PNIPAAm-CTA紅外線吸收光譜圖 71
圖4-9 不同pH值的HOOC-PAA-b-PNIPAAm-CTA高分子溶液(2 %,w/v)在λ= 450 nm下的升溫曲線(a)穿透率與溫度的關係圖 (b)穿透率對溫度的一次微分圖 74
圖4-10 不同pH值的HOOC-PAA-b-PNIPAAm-CTA高分子溶液(2 %,w/v)在λ=450 nm下的降溫曲線(a)穿透率與溫度的關係圖 (b)穿透率對溫度的一次微分圖 75
圖4-11 HOOC-PAA-b-PNIPAAm-CTA水溶液(pH 6),(1 %,w/v) (a) 15oC(b) 50oC下的粒徑分佈 77
圖4-12 不同pH值的HOOC-PAA-b-PNIPAAm-CTA高分子溶液(1 %,w/v)在不同溫度下的粒徑變化 78
圖4-13 不同pH值的HOOC-PAA-b-PNIPAAm-CTA高分子溶液(1 %,w/v)在37oC下的粒徑變化 78
圖4-15 HOOC-PAA-b-PNIPAAm-SH (MW=24700 Da)之1H-NMR光譜圖 80
圖4-16 (a) HOOC-PAA-PNIPAAm-CTA (b)HOOC-PAA-PNIPAAm-SH紅外線吸收光譜圖 82
圖4-17 Ellman's test巰基檢量線 83
圖4-18 不同pH值的HOOC-PAA-b-PNIPAAm-SH高分子溶液(2 %,w/v)在λ=450 nm下的升溫曲線(a)穿透率與溫度的關係圖 (b)穿透率對溫度的一次微分圖 85
圖4-19 不同pH值的HOOC-PAA-b-PNIPAAm-SH高分子溶液(2 %,w/v)在λ=450 nm下的降溫曲線(a)穿透率與溫度的關係圖 (b)穿透率對溫度的一次微分圖 86
圖4-20 HOOC-PAA-b-PNIPAAm-SH於90oC下pH 4(左)及 pH 7(右)環境的自組裝微胞圖 87
圖4-21 (a)不同濃度N-乙醯基葡萄醣胺標準品的一次微分吸收光譜(b) N-乙醯基葡萄醣胺檢量線 88
圖4-22 幾丁聚醣溶液在不同濃度下的還原黏度及固有黏度值 89
圖4-23 (a) HOOC-PAA-PNIPAAm-CTA (b) Chitosan(c) CS/HOOC-PAA-b-PNIPAAm-CTA (d) CS/HOOC-PAA-b-PNIPAAm-SH紅外線吸收光譜圖 91
圖4-24 CS/HOOC-PAA-b-PNIPAAm-CTA之13C-NMR光譜圖 93
圖4-25 CS/HOOC-PAA-b-PNIPAAm-SH之13C-NMR光譜圖 94
圖4-26 CS/HOOC-PAA-b-PNIPAAm-CTA複合顆粒(左)及CS/HOOC-PAA-b-PNIPAAm-SH複合顆粒(右)於90oC、 pH 6環境的自組裝圖 95
圖4-27 (a)在25oC下成長的奈米金桿(b)在28oC下成長的奈米金桿紫外光-可見光光譜圖 97
圖4-28 (a)在25oC下成長的奈米金桿(b)在28oC下成長的奈米金桿溶液 98
圖4-29 (a)在25oC下成長的奈米金桿(b)在28oC下成長的奈米金桿TEM圖 98
圖4-30 奈米金桿溶液(a)離心前與(b)離心四次後 101
圖4-31 奈米金桿離心前與離心兩次後的紫外光-可見光光譜圖 101
圖4-32 (a) HOOC-PAA-b-PNIPAAm-CTA/GNR (b) HOOC-PAA-b-PNIPAAm-SH/GNR紫外光-可見光光譜圖 102
圖4-33 (a) GNRcen*2 (b) HOOC-PAA-b-PNIPAAm-CTA/GNR (c) HOOC-PAA-b-PNIPAAm-SH/GNR 室溫靜置不同時間的紫外光-可見光光譜圖 103
圖4-34 (a) CS/HOOC-PAA-b-PNIPAAm-CTA/GNR(b) CS/HOOC-PAA-b-PNIPAAm-SH/GNR紫外光-可見光光譜圖 106
圖4-35 (a) CS/HOOC-PAA-b-PNIPAAm-CTA/GNR(b) CS/HOOC-PAA-b-PNIPAAm-SH/GNR 於室溫下靜置不同時間的紫外光-可見光光譜圖 107
圖4-36 奈米金桿溶液(a) 15oC (b) 50OC下的粒徑分佈 109
圖4-37 HOOC-PAA-b-PNIPAAm-CTA/GNR溶液(pH 6),(a) 15oC (b) 50oC下的粒徑分佈 110
圖4-38 HOOC-PAA-b-PNIPAAm-SH/GNR溶液(pH 7.4),(a) 15oC (b) 50OC下的粒徑分佈 111
圖4-39 HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR溶液(pH 6),在不同溫度下的粒徑變化 112
圖4-40 CS/HOOC-PAA-b-PNIPAAm-CTA/GNR溶液(pH 6),(a) 15oC (b) 50oC下的粒徑分佈 113
圖4-41 CS/HOOC-PAA-b-PNIPAAm-SH/GNR溶液(pH 6),(a) 15oC (b) 50oC下的粒徑分佈 114
圖4-42 CS/HOOC-PAA-b-PNIPAAm-CTA/GNR及CS/HOOC-PAA-b-PNIPAAm-SH/GNR溶液(pH 6),在不同溫度下的粒徑變化 115
圖4-43 H2O、HOOC-PAA-b-PNIPAAm-CTA/GNR及CS/HOOC-PAA-b-PNIPAAm-CTA/GNR複合材料在不同功率雷射光照射10分鐘下的光熱轉換效應之溫度關係圖(照射前之起始溫度為25oC) 116
圖4-44 CS/HOOC-PAA-b-PNIPAAm-CTA/GNR(左)及CS/HOOC-PAA-b-PNIPAAm-SH/GNR(右)於90oC、pH6環境奈米顆粒 117
圖4-46 5-Fu水溶液的檢量線圖 120
圖4-47包覆5-Fu的DRP/GNR複合載體在25oC及40oC下的累積釋放曲線 120
圖4-48包覆5-Fu的DRP/GNR複合載體在25oC及40oC下Korsmeyer-Peppas模式的藥物釋放動力圖 121
圖4-49包覆5-Fu的DRP/GNR複合載體在25oC及40oC下Higuchi模式的藥物釋放動力圖 121

表目錄
表3-1 黏度常數K與a值 58
表4-1 HOOC-PAA-CTA不同反應時間的配方 61
表4-2 HOOC-PAA-CTA高分子官能基紅外線光譜的吸收位置 63
表4-3 HOOC-PAA-CTA高分子1H-NMR光譜的吸收位置 64
表4-4 HOOC-PAA-CTA在不同反應時間的轉化率及分子量 68
表4-5 HOOC-PAA-b-PNIPAAm-CTA配方 68
表4-6 HOOC-PAA-CTA高分子1H-NMR光譜的吸收位置 69
表4-7 HOOC-PAA-b-PNIPAAm-CTA的聚合度及分子量 69
表4-8 HOOC-PAA-PNIPAAm-CTA高分子官能基紅外線光譜的吸收位置 72
表4-9 HOOC-PAA-b-PNIPAAm-SH的聚合度及分子量 81
表4-10 HOOC-PAA-b-PNIPAAm-CTA及HOOC-PAA-b-PNIPAAm-SH的巰基的含量 83
表4-11 CS/HOOC-PAA-b-PNIPAAm高分子官能基紅外線光譜吸收位置 92
表4-12 HOOC-PAA-CTA高分子1H-NMR光譜的吸收位置 94
表4-13 奈米金種晶溶液的配方 96
表4-14 成長溶液以合成奈米金桿的配方 96
表4-15 HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR複合材料的配方 100
表4-16 HOOC-PAA-b-PNIPAAm-CTA/GNR及HOOC-PAA-b-PNIPAAm-SH/GNR複合材料儲存室溫的SPL,max及吸光度變化 104
表4-17 CS/HOOC-PAA-b-PNIPAAm-CTA/GNR及 CS/HOOC-PAA-b-PNIPAAm-SH/GNR複合材料的配方 105
表4-18 CS/HOOC-PAA-b-PNIPAAm-CTA/GNR及CS/HOOC-PAA-b-PNIPAAm-SH/GNR複合材料儲存於室溫的SPL,max及吸光度變化 108
表4-19 5-Fu承載率及包覆效率 119
參考文獻 1.Jones, J. W. Enhanced Architectural and Structural Regulation Using Controlled Free Radical Polymerization Techniques; Supramolecular Assemblies: Pseudorotaxanes and Polypseudorotaxanes. Virginia Polytechnic Institute. Chap.1, 2001.
2.Hawker, C. J.; Bosman, A. W.; Harth, E. New polymer synthesis by nitroxide mediated living radical polymerizations. Chem. Rev. 2001, 101, 3661-3688.
3.Matyjaszewski, K.; Xia, J. Atom transfer radical polymerization. Chem. Rev. 2001, 101, 2921-2990.
4.Keddie, D. J.; Moad, G.; Rizzardo, E.; Thang, S. H. RAFT agent design and synthesis. Macromolecules . 2012, 45, 5321-5342.
5.Georgoussis, G.; Nikonorova, N. A.; Barmatov, E. B.; Pissis, P. Living free radical polymerization with reversible addition-fragmentation chain transfer (the life of RAFT). Polym. Int. 2000, 49, 993-1001.
6.Bawa, P.; Pillay, V.; Choonara, Y. E.; Du Toit, L. C. Stimuli-responsive polymers and their applications in drug delivery. Biomedical Materials. 2009, 4.
7.Ashammakhi, N.; Reis, R.; Chiellini, E. Topics in Tissue Engineering, Vol.3, Chap.6, 2007.
8.Benoit, D. S. W.; Gray, W.; Murthy, N.; Li, H.; Duvall, C. L. Comprehensive Biomaterials, Chap.4, 358-372, 2011.
9.Schmaljohann, D. Thermo- and pH-responsive polymers in drug delivery. Adv. Drug Deliv. Rev. 2006, 58, 1655-1670.
10.Purushotham, S.; Chang, P. E. J.; Rumpel, H.; Kee, I. H. C.; Ng, R. T. H.; Chow, P. K. H.; Tan, C. K.; Ramanujan, R. V. Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy. Nanotechnology. 2009, 20.
11.Chuang, C. Y.; Don, T. M.; Chiu, W. Y. Synthesis and properties of chitosan-based thermo- and pH-responsive nanoparticles and application in drug release. J. Polym. Sci. Part A. 2009, 47, 2798-2810.
12.Ta, T.; Convertine, A. J.; Reyes, C. R.; Stayton, P. S.; Porter, T. M. Thermosensitive liposomes modified with poly(N-isopropylacrylamide-co- propylacrylic acid) copolymers for triggered release of doxorubicin. Biomacromolecules . 2010, 11, 1915-1920.
13.Balamuralidhara, V.; Pramodkumar, T. M.; srujana, N.; Venkatesh, M. P.; Vishal Gupta, N.; Krishna, K. L.; Gangadharappa, H. V. pH sensitive drug delivery systems: A review. American Journal of Drug Discovery and Development. 2011, 1, 28-48.
14.Gao, W.; Chan, J. M.; Farokhzad, O. C. PH-responsive nanoparticles for drug delivery. Molecular Pharmaceutics. 2010, 7, 1913-1920.
15.Hu, Y.; Jiang, X.; Ding, Y.; Ge, H.; Yuan, Y.; Yang, C. Synthesis and characterization of Chitosan-poly(acrylic acid) nanoparticles. Biomaterials. 2002, 23, 3193-3201.
16.Hu, Y.; Chen, Y.; Chen, Q.; Zhang, L.; Jiang, X.; Yang, C. Synthesis and stimuli-responsive properties of chitosan/poly(acrylic acid) hollow nanospheres. Polymer. 2005, 46, 12703-12710.
17.Hu, Y.; Ding, Y.; Ding, D.; Sun, M.; Zhang, L.; Jiang, X.; Yang, C. Hollow chitosan/poly(acrylic acid) nanospheres as drug carriers. Biomacromolecules. 2007, 8, 1069-1076.
18.王三郎,生物技術,高立圖書,2000,第173-196頁
19.Aranaz, I.; Mengibar, M.; Harris, R.; Panos, I.; Miralles, B.; Acosta, N.; Galed, G.; Heras, A. Functional characterization of chitin and chitosan. Current Chemical Biology. 2009, 3, 203-230.
20.Dash, M.; Chiellini, F.; Ottenbrite, R. M.; Chiellini, E. Chitosan - A versatile semi-synthetic polymer in biomedical applications. Progress in Polymer Science (Oxford). 2011, 36, 981-1014.
21.Ravi Kumar, M. N. V. A review of chitin and chitosan applications. React Funct Polym. 2000, 46, 1-27.
22.Jayakumar, R.; Menon, D.; Manzoor, K.; Nair, S. V.; Tamura, H. Biomedical applications of chitin and chitosan based nanomaterials - A short review. Carbohydr. Polym. 2010, 82, 227-232.
23.Rinaudo, M. Chitin and chitosan: Properties and applications. Progress in Polymer Science (Oxford). 2006, 31, 603-632.
24.Dutta, P. K.; Tripathi, S.; Mehrotra, G. K.; Dutta, J. Perspectives for chitosan based antimicrobial films in food applications. Food Chem. 2009, 114, 1173-1182.
25.Shim, W. S.; Lee, D. W.; Lim, H.; Chong, H. N. Advances in Chitosan Material and its Hybrid Derivatives: A Review. The Open Biomaterials Journal. 2009, 1, 10-20.
26.Pitakpoolsil, W.; Hunsom, M. Adsorption of pollutants from biodiesel wastewater using chitosan flakes. Journal of the Taiwan Institute of Chemical Engineers. 2013.
27.Huang, X.; Neretina, S.; El-Sayed, M. A. Gold nanorods: From synthesis and properties to biological and biomedical applications. Adv Mater. 2009, 21, 4880-4910.
28.Murphy, C. J.; Gole, A. M.; Stone, J. W.; Sisco, P. N.; Alkilany, A. M.; Goldsmith, E. C.; Baxter, S. C. Gold nanoparticles in biology: Beyond toxicity to cellular imaging. Acc. Chem. Res. 2008, 41, 1721-1730.
29.Jana, N. R.; Gearheart, L.; Murphy, C. J. Wet chemical synthesis of high aspect ratio cylindrical gold nanorods. J Phys Chem B 2001, 105, 4065-4067.
30.Nikoobakht, B.; El-Sayed, M. A. Preparation and growth mechanism of gold nanorods (NRs) using seed-mediated growth method. Chemistry of Materials 2003, 15, 1957-1962.
31.Yalcın, O. Nanorods, InTech, Chap.8, 2012.
32.Link, S.; Mohamed, M. B.; El-Sayed, M. A. Simulation of the optical absorption spectra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant. J Phys Chem B. 1999, 103, 3073-3077.
33.Liu, M.; Guyot-Sionnest, P. Mechanism of silver(I)-assisted growth of gold nanorods and bipyramids. J Phys Chem B. 2005, 109, 22192-22200.
34.Murphy, C. J.; Thompson, L. B.; Chernak, D. J.; Yang, J. A.; Sivapalan, S. T.; Boulos, S. P.; Huang, J.; Alkilany, A. M.; Sisco, P. N. Gold nanorod crystal growth: From seed-mediated synthesis to nanoscale sculpting. Current Opinion in Colloid and Interface Science. 2011, 16, 128-134.
35.Tong, L.; Wei, Q.; Wei, A.; Cheng, J. -. Gold nanorods as contrast agents for biological imaging: Optical properties, surface conjugation and photothermal effects. Photochem. Photobiol. 2009, 85, 21-32.
36.Raula, J.; Shan, J.; Nuopponen, M.; Niskanen, A.; Jiang, H.; Kauppinen, E. I.; Tenhu, H. Synthesis of gold nanoparticles grafted with a thermoresponsive polymer by surface-induced reversible-addition-fragmentation chain-transfer polymerization. Langmuir. 2003, 19, 3499-3504.
37.Li, D.; He, Q.; Cui, Y.; Wang, K.; Zhang, X.; Li, J. Thermosensitive copolymer networks modify gold nanoparticles for nanocomposite entrapment. Chemistry - A European Journal. 2007, 13, 2224-2229.
38.Wei, Q.; Ji, J.; Shen, J. Synthesis of near-infrared responsive gold Nanorod/PNIPAAm core/shell nanohybrids via surface initiated ATRP for smart drug delivery. Macromolecular Rapid Communications 2008, 29, 645-650.
39.Mangeney, C.; Ferrage, F.; Aujard, I.; Artzner, V.; Jullien, L.; Ouari, O.; Djouhar Rekai, E.; Laschewsky, A.; Vikholm, I.; Sadowski, J. W. Synthesis and properties of water-soluble gold colloids covalently derivatized with neutral polymer monolayers. J. Am. Chem. Soc. 2002, 124, 5811-5821.
40.Lowe, A. B.; Sumerlin, B. S.; Donovan, M. S.; McCormick, C. L. Facile preparation of transition metal nanoparticles stabilized by well-defined (co)polymers synthesized via aqueous reversible addition-fragmentation chain transfer polymerization. J. Am. Chem. Soc. 2002, 124, 11562-11563.
41.Duwez, A. S.; Guillet, P.; Colard, C.; Gohy, J. F.; Fustin, C. A. Dithioesters and trithiocarbonates as anchoring groups for the "grafting-to" approach. Macromolecules. 2006, 39, 2729-2731.
42.Gorelikov, I.; Field, L. M.; Kumacheva, E. Hybrid microgels photoresponsive in the near-infrared spectral range. J. Am. Chem. Soc. 2004, 126, 15938-15939.
43.O'Neal, D. P.; Hirsch, L. R.; Halas, N. J.; Payne, J. D.; West, J. L. Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett. 2004, 209, 171-176.
44.Garcia, M. A.; Bouzas, V.; Carmona, N. In In Synthesis of gold nanorods for biomedical applications; AIP Conference Proceedings. 2010; 1275, 84-87.
45.Wang, C. H.; Chang, C. W.; Peng, C. A. Gold nanorod stabilized by thiolated chitosan as photothermal absorber for cancer cell treatment. Journal of Nanoparticle Research. 2011, 13, 2749-2758.
46.Guo, R.; Zhang, L.; Qian, H.; Li, R.; Jiang, X.; Liu, B. Multifunctional nanocarriers for cell imaging, drug delivery, and near-IR photothermal therapy. Langmuir. 2010, 26, 5428-5434.
47.Von Maltzahn, G.; Park, J. H.; Agrawal, A.; Bandaru, N. K.; Das, S. K.; Sailor, M. J.; Bhatia, S. N. Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas. Cancer Res. 2009, 69, 3892-3900.
48.Choi, W. I.; Kim, J. Y.; Kang, C.; Byeon, C. C.; Kim, Y. H.; Tae, G. Tumor regression in vivo by photothermal therapy based on gold-nanorod-loaded, functional nanocarriers. ACS Nano. 2011, 5, 1995-2003.
49.Riddles, P. W.; Blakeley, R. L.; Zerner, B. Reassessment of Ellman’s reagent. Methods in Enzymology. 1983,91, 49-60.
50.Riddles, P. W.; Blakeley, R. L.; Zerner, B. Ellman's reagent: 5,5'-dithiobis(2-nitrobenzoic acid) - a reexamination.Analytical Biochemistry. 1979, 94, 75-81.
51.Anitha, A.; Deepa, N.; Chennazhi, K. P.; Nair, S. V.; Tamura, H.; Jayakumar, R. Development of mucoadhesive thiolated chitosan nanoparticles for biomedical applications. Carbohydr. Polym. 2011, 83, 66-73.
52.Socrates, G. , Infrared and Raman Characteristic Group Frequencies Tables and Charts, JOHN WILEY & SONS,LTD,Third edition.
53.Didychuk, C. L.; Ephrat, P.; Belton, M.; Carson, J. J. L. Synthesis and in vitro cytotoxicity of mPEG-SH modified gold nanorods. Paper presented at the Progress in Biomedical Optics and Imaging. Proceedings of SPIE. 2008, 6856.
54.Boca, S. C.; Astilean, S. Detoxification of gold nanorods by conjugation with thiolated poly(ethylene glycol) and their assessment as SERS-active carriers of raman tags. Nanotechnology. 2010,21.
55.Orendorff, C. J.; Murphy, C. J.Quantitation of Metal Content in the Silver-Assisted Growth of Gold Nanorods. J. Phys. Chem. 2006, 110, 3990-3994
論文使用權限
  • 同意紙本無償授權給館內讀者為學術之目的重製使用,於2018-09-12公開。
  • 同意授權瀏覽/列印電子全文服務,於2018-09-12起公開。


  • 若您有任何疑問,請與我們聯絡!
    圖書館: 請來電 (02)2621-5656 轉 2281 或 來信