癌症亦稱惡性腫瘤，是一種疾病，由控制細胞生長增殖機制不正常而引起。癌細胞除了本身生長失控外，亦會侵入週遭正常組織(invasion)甚至經由體內循環系統與淋巴系統轉移至身體得其他部奮。若癌症未經治療，通常最終結果將導致死亡，在已開發國家中已成為主要死亡原因之一；因此，研發有效率的抗癌醫療與藥物傳輸系統是當今醫療科學領域的當務之急。
本研究中主要以微胞同時具有「生物可相容性」之內核，及具備「環境應答性」、「免疫迴避性」與「分子造影性」等智慧型功能之外殼，作為疏水性藥物包覆之複合型高分子微胞。利用所包覆藥物差異，形成外型截然不同的正六角型與圓球型藥物載體微胞；爾後，主要以此二種微胞為基礎來做相關的藥物傳輸研究與探討，其中包含了對抗巨噬細胞捕捉之情形、於腫瘤細胞的累積情形與細胞毒殺差異、於小鼠活體內之腫瘤組織顯影與各臟器之累積分布情形等；此研究為單純地就物性的角度來探討藥物載體微胞於生物體內的分佈狀況，與歸避體內免疫系統對於藥物載體之捕捉，並且有了初步新穎之見解，也期望以此研究能對於日後之藥物傳輸體系統與癌症治療學上盡綿薄之貢獻。
以二團聯共聚物包覆光治療藥物，藉由細胞之胞吞作用(endocytosis)將藥物送至癌細胞內進行治療效果，並於偶然之情形下，發現藥物載體之形狀並非是一般常見之圓形球載體，而是一種尚未見過的正六角型結構載體，進而引發研究之興趣。
首先，我們合成一具有生物相容性與酸鹼應答之高分子鏈段mPEG-b-P(MEA-co-VIm)，並調整不同之組成找尋最佳比例，在包覆光治療藥物Drug A1後，得到粒徑＜200nm，且粒徑分佈約為0.1，適用於動物體內藥物傳輸系統的藥物載體；藥物微胞經由TEM與AFM偵測後呈現的形狀為正六角型狀。為了確認載體形狀起因，又以同比例合成另二種高分子鏈mPEG-b-P(HPMA-co-VIm)與mPEG-b-P (EHA-co-VIm)，包覆藥物後發現形狀與上述結果相同。接著，將上述最原始的高分子鏈段mPEG-b-P(MEA-co-VIm)包覆另一種光治療藥物Drug B2，發現藥物載體為一般常見之圓球型載體，因此，證實了載體形狀之改變來自所包覆的藥物本身。
經由體外藥物釋放模擬實驗證實複合型藥物微胞於中性環境pH7.4下可以穩定地將藥物包覆。而在酸性環境pH5.0下微胞結構對環境產生應答(膨潤)可將藥物釋放出，並呈穩定釋放的效果。在材料細胞毒性研究中可知，奈米微胞由於結構組成幾乎皆為FDA 核可，故毒性較低。而光治療藥物之藥性，可經由照光與非照光之環境下，偵測藥物對於人類子宮頸癌細胞(HeLa cells)毒殺率即可知。
以共軛焦顯微鏡觀測正六角型與圓球型藥物載體分佈情形，發現小鼠肺泡巨噬細胞(MHS)對於正六角型微胞與圓球型微胞有明顯的選擇性；包覆相同藥量下，巨噬細胞對圓球型微胞之吞噬效果遠高於正六角型。若改以人類子宮頸癌細胞(HeLa cells)，則發現圓球型微胞與正六角型微胞之分佈量，幾乎相同。證實了正六角型載體微胞確實比圓球型載體微胞更容易逃離巨噬細胞之捕捉，而此現象有助於EPR效應之藥物傳輸。
在動物實驗中以optical imaging (2-D Near-IR)觀測正六角型與圓球型微胞在不同時間下於動物體內之累積量及分佈情形，實驗結果顯示具有阻撓巨噬細胞捕捉特性的之正六角型微胞相較於圓球型之下有較多藥物載體累積在腫瘤組織位置，且證實是形狀特性所造成之效果，與載體外殼材料、微胞之大小並無明顯之關連。
綜合本研究所得之結果，正六角型奈米藥物微胞無論於細胞毒性研究、共軛焦顯微鏡觀測或動物實驗均證實對於腫瘤組織累積效果均比一般圓球型微胞來得具體明顯。未來可運用此種新穎微胞之標識腫瘤組織功能，診斷癌症組織之分佈位置，於早期癌細胞擴散前追蹤與治療，並有效達到治療腫瘤效果，促進人類醫療福祉，對癌症治療醫學上作出重大貢獻。

註：1. Drug A = 5,10,15,20-Tetrekis(pentafluorophenyl)-21H,23H-porphine
2. DrugB= 5,10,15,20-Tetrakis(4-hydroxyphenyl) -21H,23H-porphine

Abstract
This study concentrates on the morphology of drug carrier and how it would effect on different endocytosis of cells. In many researches, there have demonstrated shape of drug carrier with direct relationship to avoid capture by immune system and increase efficiency of drug delivery. We invented unique self-assembly hexagonal mixed micelles by using pH sensitive diblock copolymer encapsulate photodynamic drug A (5,10,15,20-Tetrekis(pentafluorophenyl)-21H,23H-porphine). Photosensitive agent with symmetric formula tended to form crystallized aggregate. Generally, hydrophobic photosensitive agent would precipitate when it under poor solvent. By that time hydrophobic-hydrophilic diblocok copolymer encapsulated the drug A, the drug will encapsulated by polymer with hexagonal nano scale form. In contrast, drug B (5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine) loading mixed micelles were observed form as spherical particles. For bio-imaging of drug carrier, we also synthesized diblock copolymer that included Cy5.5 fluorescent dye. The characteristics and morphologies of mixed micelles were analyzed from 1H-NMR, DLS, zeta potential, AFM, and TEM.
In vitro experiment data observed hexagonal mixed micelles owned selectivity between mouse alveolar macrophage cell (MHS) and HeLa cell by confocal microscopy. They couldn’t be swallowed easily by macrophage, even if changed external surface components. Then if the drug carriers’ shape changed to spherical mixed micelles, they could be observed great amounts accumulation in macrophages and HeLa cells. The cytotoxicity of drug loading mixed micelles with hexagonal drug carriers against HeLa cell was much greater than MHS cell, but spherical drug carriers were the same. Mixed micelles accumulation and bio-distribution observed by in vivo optical imaging (Near IR) at various time. Hexagonal mixed micelles also showed more efficiency on accumulating than spherical mixed micelles on cancer cells from biodistribution analysis of mice. This study presents a new nano-scale hexagonal structure for drug carrier development. Moreover, hexagonal micelles show more efficiency than traditional spherical micelles on cancer targeting.

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