紅外線奈米粒子之合成及其應用於超音波引導腦部膠質母細胞瘤治療

Synthesis and Application of Infrared Nanoparticles Ultrasound-guided Glioblastoma Treatment in the Brain

鄭巧翎(Chiao-Ling Cheng)

指導教授 ： 劉如熹

國立臺灣大學/理學院/化學研究所/碩士(2020年)

https://doi.org/10.6342/NTU202001103

摘要

血腦屏障(blood-brain barrier)為一層由內皮細胞、星狀膠細胞與基底膜緊密連接所組成之「障壁」，可選擇性阻止某些物質由血液進入大腦內。此屏障僅可使必要之小分子物質，如，氧氣、胺基酸、葡萄糖與水通過，此屏障且將藥物與蛋白質等大分子隔絕在外。該屏障保護腦部不受病菌感染，卻亦使顱內治療難以實現。
為使藥物能有效送入腦部且治療腦內多形性腦瘤(glioblastoma，又稱膠質母細胞瘤)。本研究以可受超音波震盪產生空穴效應(cavitation)之奈米氣泡，包埋藥物並結合長餘輝奈米粒子，投遞至大腦進行腦瘤治療與追蹤。該複合材料經超音波處理後，氣泡因內部氣體介質不同於液體環境而產生空穴效應，可暫時性打開血腦屏障，將化療藥物帝盟多(temozolomide)與近紅外發光之長餘輝奈米粒子送入腦內進行藥物治療。因長餘輝奈米粒子具長時間放光與高訊雜比，其可穿透深層組織提高生物影像之解析度。於體內治療中，藉奈米複合材料治療後之腫瘤體積，較控制組減少約90％之腫瘤體積，並降低小鼠死亡率至17%，於原位治療中，藉Ki67與TUNEL組織學研判，奈米複合材料可大幅降低膠質母細胞瘤之Ki67蛋白表現且觀察其細胞凋亡現象，故本研究開發之奈米複合材料可突破血腦屏障進行藥物投遞，且能長時間追蹤腦部影像，以達有效評估腦癌之治療效果。

關鍵字

膠質母細胞瘤 ； 長餘暉奈米粒子 ； 奈米氣泡 ； 藥物傳遞

並列摘要

The blood-brain barrier (BBB) is a physical barrier composed of endothelial cells, astrocytes and the basement membrane, which can selectively prevent certain substances from crossing the blood to the brain. BBB protects the brain from germs and causes difficulty in intracranial treatment.
The nanomaterial which composed of the chemotherapy drug temozolomide (TMZ) embedded in nanobubbles (NB), persistent luminescent nanoparticles (PLN) and aptamer AS1411 (AAp) is used to treat glioblastoma. Through ultrasound induction, NBs produce cavitation that temporarily opens the BBB. In addition, PLNs release near-infrared emission and afterglow, which can penetrate deep tissues and improve the signal-to-noise ratio of bioimages. In the in vivo treatment, the tumor volume after treatment with nanocomposite material is reduced about 90% compared with the control group, and the mouse mortality rate is reduced to 17%. In the in situ treatment, Ki67 and TUNEL immunohistochemistry can be used to judge the nanocomposite material. The expression of Ki67 protein of the tumor after treatment with nanocomposite material is significantly reduced. The TUNEL can be used to observe the apoptosis of the tumor. Therefore, the nanocomposite material developed in this research can break through the BBB for drug delivery, and can track brain images for a long time to effectively evaluate the therapeutic effect on glioblastoma.

並列關鍵字

Glioblastoma ； persistent luminescent nanoparticle ； nanobubble ； drug delivery

參考文獻

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