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標題: 標靶性高分子微胞於光動力治療之應用
Cetuximab Conjugated Polymeric Micelle for Targetable Photodynamic Therapy
作者: 陳穎臻
Chen, Ying-Chen
關鍵字: 標靶
出版社: 化學系所
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摘要: 光動力治療在臨床上較傳統外科手術具有非侵入式治療的優勢,可以在特定位置持續做治療並且在治療後不易留有疤痕,並且保有原組織或器官的功能性;相反地,傳統的外科手術則必須切除病灶及周圍組織,除了容易留下大範圍的傷口及疤痕外,術後傷口的復元需要較長與較多的照護與時間,另外,組織或器官的功能性或外觀有可能因此受到影響。光動力治療為一光化學反應,係由三個基本的要素所構成,主要是由光、光感藥物、和氧氣交互作用而產生的反應,其原理主要是由光來激發光感藥物,使光感藥物和組織間的氧氣發生能量交換或是電子轉移,進而產生單態氧(Singlet oxygen, 1O2)物質或是活性氧物質(Reactive oxygen species, ROS)來達到治療的效果。目前已有多種光感藥物在臨床上被使用,像是Foscan®、Photofrin®、ALA 等,用於肺癌、皮膚癌、口腔癌、頭頸癌等治療。 單株抗體,像是cetuximab、herceptin、Bevacizumab等等,在臨床標靶癌症治療已經行之有年,單株抗體會主動標靶在特定的接受器上並使腫瘤生長受到抑制。癌細胞上常過度表現某些蛋白接受器,如大量表皮生長因子接受器(Epidermal growth factor receptor, EGFR)的癌細胞,則可使用具有選擇性的單株抗體,如cetuximab,進行標靶治療。常見的單株抗體,如cetuximab多用在轉移性大腸癌、非小細胞肺癌、頭頸癌,而herceptin多用於乳癌、乳腺癌之標靶治療。 在目前光動力治療和標靶治療,是未來癌症醫療發展的趨勢,若能結合兩者治療的優勢,期望能為癌症醫療或研究有所助益。在本篇論文中,備製cetuximab (C225)結合高分子微胞包覆光感藥物並運用在主動標靶性光動力治療上為本篇論文之目的。首先,包覆光感藥物的高分子微胞是由聚乳酸聚乙二醇之共聚物和光感藥物經由溶劑蒸發方法所製備,接著,利用改質後C225上的硫醇基和高分子微胞表面上的順丁烯二醯亞胺形成共價鍵結將C225修飾於包覆光感藥物的高分子微胞表面。此篇論文中的結果顯示,修飾了C225的高分子微胞具有良好的選擇性,並能標靶至表皮生長因子接受器過度表現的癌細胞 (A431)上,若再經由光的照射後能有效的殺死癌細胞,此系統在主動標靶性光動力治療用於癌症治療上可能具有卓越的療效。
Monoclonal antibodies, such as cetuximab(C225), herceptin, etc., have been utilized for target cancer therapy in clinic. In this study, C225 conjugated polymeric micelles with photosensitizer loading were prepared for active targeting photodynamic therapy (PDT). First, mixed micelle composed of poly(ethylene glycol)-b- poly(lactide) and maleimide-poly(ethylene glycol)-b-poly(lactide) with photosensitizer loading were prepared by solvent evaporation method. Next, the C225 antibody was conjugated to the micelle surface via thiol group and maleimide group coupling. Our results show that the photosensitizer-loaded C225-conjugated micelle can target selectively to the epidermal growth factor receptor (EGFR) overexpressed cancer cells with efficient cell killing ability after irradiation whereas most EGFR-negative cells survived under the same treatment. Thus, this active-targetable photosensitizer delivery system may have great potential for cancer therapy.
其他識別: U0005-3008201122204000
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