本研究探討胺基酸改質三團聯共聚物(OH-PLGA-PEG-PLGA-OH)在高分子微胞中疏水端內，評估其抗癌藥物輸送與合併放射線治療之效益。三團聯共聚物OH-PLGA-PEG-PLGA-OH，PLGA設計疏水鏈段，固定親水鏈段PEG，設計較短且不同莫爾比例PLGA鏈段，使得尾端基改質胺基酸效用顯著。三種胺基酸分別為鹼性應答性胺基酸(L-Histidine)、弱疏水性胺基酸(L-Tyrosine)、強疏水性胺基酸(L-Tryptophan)，由於疏水端鏈段作用力改變，其粒徑也會隨著外界環境中pH值而變化，其中Tyrosine-PLGA-PEG-PLGA-Tyrosine複合型微胞、Tryptophan-PLGA-PEG-PLGA-Tryptophan複合型微胞在體溫形成膠體，也使此類材料有機會可以做為注射型水膠在局部藥物輸送上之應用，並探討全新的 「功能性複合型奈米微胞」。 Tryptophan-PLGA-PEG-PLGA-Tryptophan複合型藥物微胞於 pH 5+5Gy radiation，可將藥物釋放出且釋放率可高達 80％以上，並呈穩定釋放的效果。Tyrosine-PLGA-PEG-PLGA-Tyrosine複合型藥物微胞於 pH 5+5Gy radiation，可將藥物釋放出且釋放率可高達 70％以上。此外，將包覆藥物之奈米微胞與子宮頸癌細胞(HeLa)、小鼠的成纖維細胞(NIH-3T3)共同培養 24 小時後，複合型藥物微胞相對於裸藥DOX 可緩慢釋放藥物。細胞胞飲之複合型藥物微胞(Tryptophan-PLGA-PEG-PLGA-Tryptophan)一段時間後照射 5Gy 放射線於對子宮頸癌細胞(HeLa)、小鼠的成纖維細胞(NIH-3T3)之細胞存活率大幅降低，因此，Tryptophan-PLGA-PEG-PLGA-Tryptophan藥物微胞具有放射線響應性。

The amino acid has been modified at the hydrophobic end of triblock copolymer (OH-PLGA-PEG-PLGA-OH) and evaluated its anticancer drug release and therapeutic effects when combined with radiotherapy. The triblock copolymer, OH-PLGA-PEG-PLGA-OH, has been evaluated with different chain length of hydrophobic PLGA and fixed chain length of hydrophilic PEG. We have to design the short hydrophobic chain of PLGA and therefore the effects of tail amino acid can be examined. So, the three types of amino acids were basic based L-Histidine, hydrophobic L-Tyrosine and hydrophobic L-Tryptophan. Owing to molecule interaction in the hydrophobic chain, its particle size also changed with the pH value of the external environment. Tyrosine-PLGA-PEG-PLGA-Tyrosine and Tryptophan-PLGA-PEG-PLGA-Tryptophan formed stable micelles at low temperatgel and become the hydrogel at body temperature, which provides opportunities for these materials to be used as injection hydrogels for local drug delivery.
The drug release from the Tryptophan-PLGA-PEG-PLG micelles shwed 80% at pH 5 with 5 Gy radiation. However, the less drug release from Tyrosine-PLGA-PEG-PLGA-Tyrosine around 70% of drugs at pH 5 with 5 Gy radiation. When drug-encapsulated micelles and co-cultured with HeLa cervical cancer cells and NIH-3T3 mouse fibroblasts for 24 h, the drug could slowly release from the micelle, which hae been evaluated by fluroscence micrscopy. Finally, the viability of HELA and NIH-3T3 cells decreased when the drug loaded Tryptophan-PLGA-PEG-PLGA-Tryptophan micelles has been endocytosis and treated with 5 Gy of radiation. The tryptophan modified PLGA-PEG-PLGA has been proved to have themrals responsive sol-gel trasition effect and capable to responsive with external gamma radiation to let the loaded drug released from carrier.

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