癌症的死亡率和發病率在世界範圍內都在迅速上升，癌症已然成為世界第
三大的死因。近年研究顯示出腫瘤與正常細胞周圍的環境非常不同，腫瘤的微
環境特徵包含酸性、缺氧、過度生長和高濃度的活性氧化物。針對這些特別的
腫瘤為環境特徵，標靶治療會是不錯的治療策略，相比與傳統的化學治療，標
靶治療較低的副作用、低毒性等諸多優點，因此標靶治療最有潛力的癌症治療
手段。
本論文主要合成一種以 selenium 作為疏水端，並且與 PEG(親水端)形成交
聯共聚的高分子藥物載體，利用具活性氧化物(Reactive Oxygen Species, ROS)應
答的 selenium 在載體內部形成交聯內核。由於 selenium 內核與抗癌藥阿黴素
(doxorubicin, DOX)之間形成 π–π 重疊，使 DOX 所形成之奈米粒子的包覆率與
包覆效率分別提高至 5.65%與 69.29%。由 DOX 藥物釋放的結果來看，在模擬腫
瘤高濃度 ROS 的環境下，在 24 小時釋放抗癌藥物 DOX 所得之積累量為 30%，
72 小時後增加至 52%。體外細胞毒性測試結果顯示，未加載藥物的高分子奈米粒
子與海拉細胞(腫瘤細胞)與纖維細胞(正常細胞)共存 24 小時後，細胞的存活率
皆大於 80%，證明高分子擁有良好的生物相容性，而加載藥物的高分子奈米粒子
與海拉細胞共存 24 小時後，細胞存活率下降至 40%，表明藥物載體具有較佳抗
癌的活性。細胞攝取的結果顯示，加載抗癌藥物的高分子奈米粒子與海拉細胞共
存 12 小時後，細胞核內 DOX 螢光強度高，近一步確認高分子奈米粒子可有效
進入癌細胞內部，並有效殺死癌細胞。

Recent research has revealed that the microenvironmental properties of tumors
differ significantly from those of normal cells, including acidity, hypoxia, overgrowth,
and high levels of reactive oxides. Thus, targeted treatment approaches offer several
advantages over regular chemotherapy because of these parameters, such as fewer side
effects, accurate administration, and low toxicity. As a result, the most promising cancer
treatment is targeted therapy.
In this paper, we concentrate on the synthesis of a polymeric drug carrier using
selenium as the hydrophobic component, which is subsequently cross-copolymerized
with PEG (hydrophilic end). The selenium with a ROS response is employed to
fabricate a cross-linked inner core within the carrier. The encapsulation rate and
effectiveness of the nanoparticles were enhanced from 5.65 % to 69.29 % due to the
substantial overlap between the inner core of selenium and the anti-cancer medication
doxorubicin (DOX).
Drug release studies revealed that the accumulation of DOX was 50% after 24
hours and escalated to 90% after 72 hours in a simulated tumor environment with high
ROS levels. In vitro cytotoxicity experiments indicated that unloaded polymer
nanoparticles survived with Hela cells (tumor cells) and fibroblasts (normal cells) for
more than 80 percent of the time, confirming the polymer's high biocompatibility. The
cell survival rate reduced to 40% after 24 hours of cohabitation of the drug-loaded
iii
polymer nanoparticles with Hela cells, demonstrating that the drug carriers had greater
anti-cancer effectiveness. The cellular uptake results suggests that the DOX
fluorescence intensity in the nucleus was high after 12 hours of existence between the
drug-loaded polymer nanoparticles and Hella cells, confirming that the polymer
nanoparticles could efficiently infiltrate and kill cancer cells.

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