| 摘要: | 微生物在生活中被廣泛應用，例如汙水處理使用各類微生物來分解有機廢物或是重金屬，利用厭氧菌來製造醇類，醫學上也有利用細菌進行治療的細菌癌症療法。但不可避免的在作用環境中總有不利於微生物生存的條件存在，像是水中可能含有抗菌劑、厭氧菌作用環境無法完全阻隔氧氣、病人體內的溶菌酶和抗生素等，都會減弱微生物的活性及存活能力。因此科學家便致力於研究有機或無機材料結合生物體的生物複合材料，來增強生物細胞對於環境壓力的適應性。
金屬有機骨架材料 (MOFs)，可藉由調整金屬離子與有機配體，根據需求調整其孔洞性質、比表面積、化學穩定性等，具有相當的多樣性，因此近期常被應用於與生物系統結合之研究。
本研究藉由將類沸石咪唑骨架材料-90 (ZIF-90) 包覆大腸桿菌 (Escherichia coli, E. coli) 表面形成單一晶體包覆大腸桿菌 (E. coli@ZIF-90)，以及將類沸石咪唑骨架材料-8 (ZIF-8) 合成於大腸桿菌表面形成塗層 (E. coli⊂ZIF-8)的產物，並於高溫環境中來探討E. coli@ZIF-90與E. coli⊂ZIF-8兩者不同包覆情況對提高大腸桿菌耐熱能力的影響。同時也以這兩種生物複合材料進行了與細胞癌症療法相關的體外細胞實驗：透過誘發巨噬細胞活化生成而得的多種細胞激素(Cytokines)，探討這兩種生物複合材料於誘發細胞免疫反應的多寡；以及將E. coli@ZIF-90與不同pH值環境下的巨噬細胞一同培養，觀測材料是否有崩解現象及大腸桿菌釋放後與細胞是否有作用力，探討ZIF-90材料作為大腸桿菌載體的潛力。以期待未來將本研究成果應用於癌症治療之可行性以及在癌症治療領域帶來更進一步的突破。;Microorganisms are widely used in life. For example, decomposing organic waste in sewage, producing alcohol by anaerobic fermentation, besides, bacteria can also be used in cancer treatment called “bacteria cancer therapy”. However, there are always some factors which will threaten their survival. Antiseptics exist in water, oxygen exist in the media of anaerobic bacteria, lysozyme and antibiotics in patients. These conditions all make microorganisms deactivate. Therefore, scientists research on combining organic or inorganic materials with cells in order to enhance their adaptability toward environmental stress.
Metal organic frameworks (MOFs) have variable pore properties, specific surface area, chemical stability. Scientists can adjust these properties by changing the precursors to fit their purpose. Therefore, the development of biocomposites by combinig Metal-organic frameworks and living systems is rapidly emerging.
In this study, we successfully synthesized two kinds of biocomposites, Escherichia coli (E. coli) cells was encapsulated into single crystal zeolitic imidazolate framework-90 (ZIF-90) or been coating by zeolitic imidazolate framework-8 (ZIF-8). After these combinations, E. coli gains the ability to survive the treatment of heat. E. coli can still regrowth after removing the material. At the same time, we studied whether these E. coli biocomposites will determine the activation of macrophages. The induced expression of inflammatory cytokines was evaluated using a mouse inflammation antibody array. E. coli@ZIF-90 significantly prevented the release of inflammatory mediators from E. coli compared to free E. coli and E. coli⊂ZIF-8.
On the other hand, ZIF-90 also had the incredible performance on being a delivery carrier. We found out the bacteria phagocytosis was observed though the incubation with E. coli@ZIF-90 in pH 6.0 culture media, simulated the environments of the cancer cells compared to E. coli@ZIF-90 were no decomposed in pH 7.0 media. This study may pave the new way in the history of bacterial cancer therapy and hope this study will be the “carrier” in bacterial cancer therapy. |
