本研究中，我們利用雙乳化法製備出具有光熱敏感性之乳鐵蛋白(lactoferrin, Lf)修飾
豌豆型的藥物傳輸系統，組成包括氧化石墨烯(GO)與聚乙烯醇(PVA)。合成過程中，
PVA 的雙性特性，在油水介面中能夠形成奈米微胞，並包覆大量油相藥物；而 GO
可大量吸附 PVA 微胞，在自組裝的過程中形成棒狀結構。GO 與 PVA 組成的複合材
料已被證實可以增強其材料的機械性質，呈現高穩定的特性。此外，GO 能扮演光熱
效應轉換者，而奈米豌豆還可以載負大量的疏水性抗癌藥物:歐洲紫杉醇(Docetaxel,
DTX)，化療藥物的包覆率也可以達七成以上，並且在雷射的刺激之下造成藥物釋放。
再者，奈米豌豆外修飾的乳鐵蛋白(Lf)更能進一步增加藥物載體的累積到 RG2 癌細
胞。在細胞實驗中，可以發現，結合標靶性光熱及化學協同治療對於癌細胞的毒殺
能力，比單獨化學治療強 2.4 倍，比光熱及化學協同治療強 1.6 倍。而在動物實驗
中，在照射進紅外光雷射 15 分鐘後，更可以摧毀癌細胞並抑制復發。因此，奈米豌
豆是一個有潛力的藥物傳輸平台，且具有光敏性與標靶性，並結合光熱及化學協同
治療功效，期許能在腫瘤治療或其他生醫領域有更多方面性的運用。
關鍵字: 標靶性光熱及化學協同治療、雙乳化法、氧化石墨烯、乳鐵蛋白、歐洲紫
杉醇

A novel photo-responsive lactoferrin (Lf)-coated nanopea that used as a photothermal agent with
pea-like structure was constructed by anchoring graphene oxide nanosheets on polymer surfactant
(polyvinyl alcohol, PVA) shell through double emulsion approach. These graphene oxide-PVA
based composites were confirmed that could enhance their mechanical performance for
nanocomposite. These nanopea can transport fully concealed hydrophobic anticancer drug
Docetaxel (DTX) (EE: 71.7％), in the core to be later unloaded by heat triggered by near-infrared
irradiation. Furthermore, Lf- modified nanopea could significantly enhance the accumulation of
nanopea in RG2 cells and successfully deliver drugs into targeted cancer cells. The experiment of
in vitro, targeted chemophotothermal therapy by Lf-Nanopea/DTX performs 2.4-fold and 1.6-fold
higher therapeutic efficacy than single chemotherapy and chemophotothermal therapy, respectively.
In vivo, following a single 15 min NIR irradiation, the photo-chemo-thermal therapy of nanopea
eradicates tumor cells not only in the light-treating area but also widely light-omitted tumor cells,
overcoming the cancer cells recurrence due to efficient cell killing efficacy. These results
demonstrate that the nanopea is a potential new drug delivery platform for local-targeting, photo-
responsive, combined chemotherapy/hyperthermia for tumor treatment and other biomedical
applications.
Key words: targeted chemophotothermal therapy, double emulsion method, graphene oxide,
lactoferrin, Docetaxel

iii

Contents
中文摘要 ............................................................................................................................... i
Abstract ............................................................................................................................... ii
Contents ............................................................................................................................ iii
LIST OF SCHEMES .......................................................................................................... v
LIST OF TABLES ............................................................................................................. vi
LIST OF FIGURES ......................................................................................................... vii
Chapter 1 Introduction ...................................................................................................... 1
Chapter 2 Literature Review and Theory ....................................................................... 4
2.1 Nanoparticles for cancer therapy ........................................................................... 4
2.1.1 Nanoparticle size ......................................................................................... 5
2.1.2 Nanoparticle shape ...................................................................................... 6
2.1.3 Nanoparticle surface chemistry ................................................................... 8
2.1.4 Graphene oxide on cancer therapy .............................................................. 9
2.2 Graphene-based nanocomposites for drugs and genes delivery .......................... 10
2.3 Graphene-based nanocomposites for photothermal therapy ................................ 16
2.4 Graphene-based nanocomposites for combined chemo-photothermal therapy ... 23
Chapter 3 Materials and methods .................................................................................. 31
3.1 Material ................................................................................................................ 31
3.2 Apparatus ............................................................................................................. 33
3.3 Method ................................................................................................................. 34
3.3.1 Synthesis of Graphene oxide .................................................................... 34
3.3.2 Synthesis of Lf-modified Nanopea ........................................................... 34
3.3.3 Characterization ........................................................................................ 35
3.3.4 Photothermal heating effect of nanopea .................................................... 36
3.3.5 Drug loading and drug encapsulation efficiency ...................................... 36
3.3.6 In Vitro Release ......................................................................................... 36
3.3.7 Cell culture ................................................................................................ 37
3.3.8 Cell vability assay ..................................................................................... 37
3.3.9 Cellular uptake of nanopea capsules ......................................................... 38
3.3.10 Targeting ability of the Lf-Nanopea capsules was quantified by flow
cytometry ........................................................................................................... 38
3.3.11 In vitro Live/Dead cell imaging after NIR irradiation ............................ 39
3.3.12 In vivo experiments ................................................................................. 39
Chapter 4 Results and Discussions ................................................................................. 41
4.1 Synthesis and characterization of nanopea capsule ............................................. 41
4.2 Photothermal effect, drug loading capacity and NIR light-triggered drug release of nanopea capsules ................................................................................................... 48
4.3 Cytotoxicity and cell uptake of nanopea capsules ............................................... 54
4.4 In vitro chemo-photothermal therapy of nanopea capsules ................................. 57
4.5 In vivo animal experiment ................................................................................... 61
Chapter 5 Conclusions ..................................................................................................... 69
Reference........................................................................................................................... 70

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