Mitomycin-C (MMC) 在臨床上被用來治療包括胃癌、乳癌、子宮頸癌等等癌症，但其細胞毒殺作用不具專一性，且會造成骨髓抑制、黏膜炎及掉髮等副作用。在治療膀胱癌病患時，在膀胱內灌注高濃度的Mitomycin-C，使抗癌藥物在膀胱內直接作用於膀胱癌，殺滅膀胱內癌細胞，包括膀胱切除術後的殘餘癌細胞。然而即使用這種局部化療的方式來治療膀胱癌，病患仍然會產生不等程度的化療副作用。因此，本論文將著重於利用PAMAM發展新的Mitomycin-C粒子，來改善傳統Mitomycin-C的藥物劑量以及希望提高細胞毒殺效果。本論文研究分為兩個部分，第一部分為使用Poly（amidoamine）（PAMAM） 進行對Mitomycin-C藥物包埋，這種載體具有低毒性以及不易引起體內激烈免疫系統反應之優點，而且PAMAM容易被細胞所吞噬，以達到快速吸收的成效。本部分將探討以不同方式混合PAMAM與Mitomycin-C之包覆率，並以電子顯微鏡以及分光光度計分析其包覆效果。實驗結果顯示，在室溫下以50ppm旋轉四十八小時，可以達到PAMAN與Mitomycin-C之最大包埋率約為百分之五十二。第二部分為設計並合成以PAMAM 為核中心結構之PAMAM-MMC複合物系統，用來做藥物殘留時間以及膀胱癌細胞毒殺實驗，進一步再分析PAMAM-MMC複合物系統對膀胱癌細胞之細胞週期的影響。實驗結果顯示，PAMAM-MMC複合物作用於膀胱癌細胞的藥物殘留量比單獨未包覆PAMAM之Mitomycin-C的殘留量多了約百分之二十二，而且在藥物毒殺試驗中，無論是高濃度或低濃度之PAMAM-MMC複合物都比相同濃度之Mitomycin-C有著更顯著的差異。此外在四十八小時的藥物毒殺之下，PAMAM-MMC複合物造成細胞凋亡的效應也比Mitomycin-C來得高。

Mitomycin-C (MMC) is a clinical practice for the treatment of cancer, including gastric cancer, breast cancer, cervical cancer. However, its cytotoxicity does not specify only on cancer cell, but can also cause bone marrow suppression, mucositis, hair loss and other side effects. In the treatment of bladder cancer, patients were injected intravesical MMC at high concentrations to their bladder, letting the anti-cancer drugs work directly on bladder cancer cells and kill them, including the residual cancer cells after bladder resection surgery. However, even this local chemotherapy treatment to bladder cancer would still cause different degrees of side effects to the patient. Therefore, our thesis will focus on developing the new MMC Particle strategies to improve the traditional MMC drug dosage as well as enhance the effect of cell cytotoxic.
This thesis divides into two parts, the first part is to use Poly (amidoamine) (PAMAM) to wrap the MMC drugs. This carrier has the characteristics of low toxicity and the advantage of preventing body from intensive reaction by the immune system. Furthermore, PAMAM is easy to be swallowed up by cells, so it can be absorbed effectively and rapidly. This section will discuss the binding effect of mixing PAMAM and MMC in different ways, and the results will be analyzed by the electron microscope and spectrophotometer. In our research, we found that the results shown at room temperature can reach maximum binding of PAMAM-MMC conjugate rate of about fifty-two% by rotating forty-eight hours in 50ppm.
The second part is to design and synthesize the PAMAM-MMC conjugate system with PAMAM as the nuclear core to carry out the ethe test of drug residue time and bladder cancer cell cytotoxicity experiments, which can then analyze the influence of PAMAM-MMC conjugate against human bladder cancer cell cycle. The results shows that the quantity of drug residue in bladder cancer cells is 22% higher in using PAMAM-MMC conjugate than in using separated unbound PAMAM- MMC drugs. Moreover, in trials of drug poisoning, high concentration or low concentration of PAMAM-MMC conjugate have more prominent differences than the MMC at same concentration. In addition, under forty-eight hours of drug poisoning, the effect of apoptosis cause by the PAMAM-MMC conjugate is much stronger by the MMC as well.

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