1,720,959 research outputs found
ynthesis of inorganic nanoparticles/organic alginate composite for guiding chemotherapy of bladder cancer
No full text 本研究的目的是將具有高生物相容性和表面修飾官能基的有機海藻酸與各種功能性的無機奈米粒子（包含氫氧基磷灰石、氧化鐵、硼酸鈣和類沸石咪唑骨架材料）結合，應用於生醫領域。本研究包含海藻膠微米粒子與海藻膠奈米粒子兩種類型的複合材料，分別是利用空氣動力噴霧法（air dynamical atomization）合成搭載蛋白質與氫氧基磷灰石的海藻膠微米球（LSZ-HA@Alg）；另外則是結合預凝膠（pre-gel）和共沉澱法（co-precipitation）合成一系列無機／海藻膠奈米粒子，且能進一步合成無機殼層結構，包含CaBO3@Alg、ZIF-8@Alg和Fe3O4@CaP-Alg。海藻酸提供粒子形成時的穩定性，改善以往共沉澱法造成粒子大小差異性大且團聚等缺點，並且提供羧酸基以修飾標靶分子，其中修飾c(RGDfK)的Fe3O4@CaP-Alg-RGD用於標靶人類膀胱癌細胞T24。
Fe3O4@CaP-Alg具有Fe3O4的超順磁特性，而磷酸鈣殼層形成時能同步包覆抗癌藥Doxorubicin，包覆效率約為80 %。利用ICP-OES量測，修飾c(RGDfK)的複合材料於T24中的Fe3O4累積量相較於為修飾前提升3.13倍，代表此複合材料具有標靶細胞的功能。而搭載藥物並接上標靶分子後的Fe3O4@CaP(+)-Alg-RGD比起free doxorubicin更容易進入細胞而達到毒殺效果，相對細胞存活率依材料濃度的不同降至0.1-0.3之間。同時能藉由磁場導引材料至特定位置，提高局部位置的材料濃度，在不傷害周邊細胞的情形下，對於癌細胞有更好的抑制效果，達到誘導化學治療之功效。The purpose of this study is to fabricate a composite consisting of organic alginate and inorganic nanoparticles (including hydroxyapatite, Fe3O4, CaBO3, and ZIF-8) for biomedical applications. There are two types of composites synthesized in this study: (1) alginate-based microspheres and (2) alginate-based nanoparticles. For the part of alginated-based microspheres, proteins and hydroxyapatite nanoparticles can be encapsulated into alginate microspheres with diameters around 20-30 μm (named as LSZ-HA@Alg) via air dynamical atomization method. For the part of alginated-based nanoparicles, inorganic nanoparticles such as Fe3O4 and CaP were synthesized within the organic alginate polymer through a combination of pre-gel method and co-precipitation. We then functionalize Fe3O4@CaP-Alg nanocomposite with c(RGDfK) peptide for targeting bladder cancer cell line (i.e. T24). Fe3O4@CaP-Alg nanocomposite exhibits superparamagnetic property of Fe3O4, and the CaP shell can encapsulate an antitumor drug, doxorubicin with an encapsulation efficiency of about 80 %. With ICP-OES measurements, the accumulation of Fe3O4 in T24 for Fe3O4@CaP-Alg-RGD is 3.13 times more than that of Fe3O4@CaP-Alg, indicating the cell targeting ability. Furthermore, the relative cell viabilities decrease to 0.1-0.3, depending on the concentration of Fe3O4@CaP(+)-Alg-RGD. We can use magnetism to guide the synthesized nanocomposite to specific locations that can increase the local concentration of material and result in better inhibition of the cancer cell with the lowest impact on adjacent cells, which would be useful for guiding chemotherapy of bladder cancer.目錄
英文摘要 i
中文摘要 iii
致謝 iv
目錄 v
圖目錄 ix
表目錄 xiii
第一章 緒論 1
第二章 文獻回顧 3
2-1藥物載體（drug carriers） 3
2-1-1藥物載體的需求 3
2-1-2載體於生物系統 4
2-2新型載體或製劑 6
2-2-1含硼試劑（boron delivery agent） 6
2-2-2磷酸鈣（calcium phosphate） 8
2-2-3氧化鐵（iron oxide） 9
2-2-4類沸石咪唑骨架材料（zeolitic imidazolate framework） 11
2-3海藻酸（alginate） 15
2-3-1海藻酸的性質 15
2-3-2海藻酸成膠方式 16
2-3-3海藻膠顆粒的製備 18
2-3-4預凝膠（pre-gel）法 19
2-3-5海藻酸-無機複合材料及應用 20
2-4 膀胱癌（bladder cancer） 25
2-5標靶療法（target therapy） 26
2-5-1被動式標靶 26
2-5-2主動式標靶 26
2-6表面修飾（surface modification） 29
2-6-1常見表面修飾方法 29
2-6-2 EDC/NHS 31
第三章 研究動機與目的 33
第四章 實驗方法 34
4-1實驗藥品 34
4-2實驗儀器 36
4-3材料製備 37
4-3-1實驗總流程 37
4-3-2 HA@Alg微米顆粒製備 38
4-3-3硼酸鈣／海藻膠奈米粒子（CaBO3@Alg）製備 40
4-3-4 ZIF-8／海藻膠奈米粒子（ZIF-8@Alg）製備 41
4-3-5氧化鐵－磷酸鈣核殼（core-shell）結構／海藻膠奈米粒子（Fe3O4@CaP-Alg） 42
4-3-6 Fe3O4@CaP-Alg／Fe3O4@CaP(+)-Alg接上RGD peptide 43
4-4材料性質分析 45
4-4-1光學／螢光顯微鏡 45
4-4-2動態光散射粒徑及界面電位分析儀 45
4-4-3掃描式電子顯微鏡（SEM） 46
4-4-4穿透式電子顯微鏡（TEM） 46
4-4-5傅立葉轉換紅外吸收光譜（FTIR） 46
4-4-6感應耦合電漿原子發射光譜儀（ICP-OES） 46
4-4-7 X光繞射儀（XRD） 46
4-4-8超導量子干涉磁量儀（SQUID） 47
4-4-9紫外光可見光譜儀（UV-Vis） 47
4-4-10光激發螢光光譜儀（PL） 47
4-5 Fe3O4@CaP(+)-Alg藥物之釋放 47
4-6細胞實驗 48
4-6-1生物相容性與相對細胞存活率測試 48
4-6-2感應耦合電漿原子發射光譜儀（ICP-OES） 49
4-6-3顯微鏡實驗 50
第五章 結果與討論 52
5-1包覆HANPs之海藻膠微米顆粒（HA@Alg） 52
5-1-1材料性質 52
5-1-2 搭載模擬蛋白溶菌酶 58
5-1-3 生物相容性測試 61
5-2硼酸鈣／海藻膠奈米粒子（CaBO3@Alg） 61
5-2-1材料性質 62
5-2-2含硼量測定 66
5-2-3生物相容性測試 66
5-3 ZIF-8／海藻膠奈米粒子（ZIF-8@Alg） 67
5-3-1材料性質 67
5-3-2搭載模擬藥物R6G 72
5-3-3生物相容性測試 72
5-4氧化鐵－磷酸鈣核殼結構／海藻膠奈米粒子（Fe3O4@CaP-Alg） 73
5-4-1材料性質 74
5-4-2搭載藥物Dox與釋放測試 84
5-4-3細胞實驗 90
第六章 結論 97
第七章 未來展望 98
第八章 參考文獻 99
附錄 A
附錄A 以共沉澱法製備硼酸鈣奈米粒子（CaBO3） A
附錄B Fe3O4@CaP-Alg的TEM-EDS定性分析
Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene
Get PDFThe first synthesis of 2-iodoynamides is described as well as the first [2+2] cycloadditions of ketene with iodo alkynes.National Institutes of Health (U.S.) (GM 28273)Boehringer Ingelheim PharmaceuticalsMerck Research Laboratorie
Benzannulation via the Reaction of Ynamides and Vinylketenes. Application to the Synthesis of Highly Substituted Indoles
No full textA two-stage “tandem strategy” for the synthesis of indoles with a high level of substitution on the six-membered ring is described. Benzannulation based on the reaction of cyclobutenones with ynamides proceeds via a cascade of four pericyclic reactions to produce multiply substituted aniline derivatives in which the position ortho to the nitrogen can bear a wide range of functionalized substituents. In the second stage of the tandem strategy, highly substituted indoles are generated via acid-, base-, and palladium-catalyzed cyclization and annulation processes.National Institutes of Health (U.S.) (Grant GM28273)National Science Foundation (U.S.) (Grant CHE-1111567)Merck Research LaboratoriesBoehringer Ingelheim PharmaceuticalsEli Lilly and Company (Graduate Fellowship)Massachusetts Institute of Technology. Dept. of Chemistry (C.P. Chu and Y. Lai Fellowship Fund
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Batch and Flow Photochemical Benzannulations Based on the Reaction of Ynamides and Diazo Ketones. Application to the Synthesis of Polycyclic Aromatic and Heteroaromatic Compounds
No full textavailable in PMC 2014 November 1Highly substituted polycyclic aromatic and heteroaromatic compounds are produced via a two-stage tandem benzannulation/cyclization strategy. The initial benzannulation step proceeds via a pericyclic cascade mechanism triggered by thermal or photochemical Wolff rearrangement of a diazo ketone. The photochemical process can be performed using a continuous flow reactor which facilitates carrying out reactions on a large scale and minimizes the time required for photolysis. Carbomethoxy ynamides as well as more ketenophilic bis-silyl ynamines and N-sulfonyl and N-phosphoryl ynamides serve as the reaction partner in the benzannulation step. In the second stage of the strategy, RCM generates benzofused nitrogen heterocycles, and various heterocyclization processes furnish highly substituted and polycyclic indoles of types that were not available by using the previous cyclobutenone-based version of the tandem strategy.National Institutes of Health (U.S.) (GM 28273)National Science Foundation (U.S.) (CHE-1111567)Boehringer Ingelheim PharmaceuticalsAstraZeneca (Firm) (Graduate Fellowship)Massachusetts Institute of Technology (George Buchi Summer Fellowships)Massachusetts Institute of Technology (Merck Fellowship)Massachusetts Institute of Technology (David A. Johnson Fellowship)Massachusetts Institute of Technology (C. P. Chu and Y. Lai Fund)Merck Research Laboratorie
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
