製備無機奈米粒子/有機海藻膠之複合材料於膀胱癌之誘導化學治療

ynthesis of inorganic nanoparticles/organic alginate composite for guiding chemotherapy of bladder cancer

王毓璞(Yu-Pu Wang)

指導教授 ： 吳嘉文

國立臺灣大學/工學院/化學工程學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.10687

摘要

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。

關鍵字

空氣動力噴霧法 ； 預凝膠 ； 海藻酸 ； 誘導化學治療 ； 膀胱癌

並列摘要

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.

並列關鍵字

air dynamical atomization ； pre-gel ； alginate ； guiding chemotherapy ； bladder cancer

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