多形性膠質母細胞瘤(Glioblastoma, GBM)是最致命且常見的腦癌，由於GBM的高浸潤性，因此手術時醫生難以判斷腫瘤邊界導致切除不完整而有高復發率。為了改善此問題，5-ALA被應用於GBM螢光影像引導手術，於2017年被FDA核准為醫療用藥，然而其代謝物PPIX的螢光訊號有光漂白問題，除了可能影響手術中影像穩定度外也難以搭配光動力治療與光熱治療等光療法。因此無嚴重光漂白問題且有光熱治療效果的拉曼標記有潛力取代螢光標記應用於GBM的影像引導光熱治療手術中。

此論文目的為：1.開發有機會取代螢光標記的拉曼標記以降低光漂白問題。2.利用拉曼標記的表面電漿共振特性在GBM腦癌細胞上實現專一性拉曼訊號加上光熱治療效果。

實驗室所開發的拉曼標記以核心-衛星金粒子叢集結構為基底，外部包覆二氧化矽保護殼並修飾對Epidermal growth factor receptor (EGFR)有專一性的抗體，此種核心-衛星金粒子叢級結構內部間隙能產生熱點效應將拉曼訊號有效增強約10^8倍，透過表面電漿共振能將吸收峰值波長的光能有效轉換為熱能，因此有潛力對過度表現EGFR的GBM細胞進行專一性拉曼訊號加上光熱治療。

此論文重要的成果為：1.開發出拉曼強度只差螢光約一個數量級的拉曼標記。2.相同曝光條件下拉曼標記的拉曼訊號半衰期約為螢光分子訊號的3-5倍。3.以此標記在大鼠GBM腦癌細胞與大鼠腦正常細胞共培養的環境中做出活細胞拉曼訊號專一性與光熱治療專一性。上述驗證實驗室所開發的粒子有應用到GBM拉曼訊號引導光熱治療實驗的潛力，但粒子的專一性與光熱治療效果仍有待優化。

目前尚未有團隊做出對GBM細胞與正常細胞共培養的拉曼訊號引導光熱治療實驗，因此若後續有對專一性與光熱治療效果優化，將有機會成為領域中具有突破性的研究。

Glioblastoma(GBM) is the most fatal and common brain tumor. GBM is highly infiltrative and difficult to be completely removed during surgery. The only commercial contrast agent, 5-ALA, for GBM fluorescent image guided surgery suffer from photobleaching problems which may affect the stability of image. Raman tags based on localized surface plasmon resonance (LSPR) have strong Raman signals, photo-thermal therapy effect and less photobleaching problems. Therefore, there is great potential for Raman tags to replace fluorescent tag and be developed for Raman guided photothermal therapy for GBM.

In the previous works of our lab, the EGFR-specific Raman tag based on core-satellite-assemblies(CSA) of gold nanoparticles was developed which could enhance the Raman signal to 10^8 times at the intra-nanogap theoretically .

In this work, the purposes are to optimize the functions of CSA-based Raman tags and verify if it could distinguish the GBM cells locations and treat the GBM cell through photothermal therapy. To optimize the structure stability, photothermal efficiency, Raman intensity and spectrum features, 3 generations of Raman tags were developed. The last generation of Raman tags which combined the functions from above generations has specificity of live cell Raman signal and photothermal therapy for GBM cells but there is still room for the specificity to improve.

In conclusion, the CSA-base tags with photothermal effect and strong Raman signal were developed and the potential of application of Raman guided photothermal therapy is demonstrated but there is still room for the specificity to improve.

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