X光致螢光奈米粒子在光動力治療腦癌之研究

Abstract

惡性腦瘤因局部浸潤及局部復發對人類健康、生活造成極大的威脅。其預後由手術切除範圍而定，然而腫瘤的組織浸潤常造成病灶邊界不明顯，導致其難以根除。光動力治療提供標靶性的治療，能降低復發率，在副作用最低的情況下提升存活率，具有治療腦癌不二選擇的潛力。然而腦癌的光動力治療仍需在開顱手術下照射外接光源進行，術後的顱壓升高、腦水腫等症狀一直是開顱無可避免的併發症。本研究發展一能藉由能量較高，穿透力較深之X光激發放出可見光之奈米粒子，以三氟化鑭為基體，摻雜鋱為發光中心。在維持奈米尺寸的條件下，將材料表面利用金及聚乙二醇修飾後，接枝葉酸及光動力藥物中-四(4-羧基苯基)卟吩(Meso-tetra(4-carboxyphenyl) porphine, MTCP)，可進一步提高腫瘤中藥物累積量。在生物相容性測試下，三氟化鑭本身不影響細胞活性及細胞增生，而在x光照射三氟化鑭後激發光敏物質而抑制神經膠細胞瘤增生。接枝葉酸後的材料，經由電子顯微鏡也證實了癌細胞確實將其包吞入內。此材料在搭配以x光為激發射源的光動力治療下，具備腦癌治療的潛力。如此一來，光動力治療便不再受傳統光源穿透深度限制，也毋須承擔開顱後的風險，又非侵入式療法，更能提升治療品質。

Owing to local invasion and local recurrence, the outcomes of brain tumors are poor. Their prognosis is highly dependent on the degree of surgery resection; however, the margin of tumor is hard to define due to tissue invasion. Photodynamic therapy appears as a promising treatment modality, yet it is restricted by the short penetration of light source. Therefore, as for brain cancer treatment, the whole procedure should be done during craniotomy. We try to investigate LaF3:Tb, a luminescence nanoparticle; use its emission light triggered by X-ray to excite Meso-tetra(4-carboxyphenyl) porphine (MTCP), the photosensitizer, and then leads to photodamage to tumor cells. The LaF3:Tb nanoparticle is a biocompatibility nanomaterial; shows no significant influence in 3T3 cell viability and proliferation. The 9L gliosarcoma cells with LaF3:Tb and MTCP exhibit decreased viability under the X-ray irradiation. By means of Au coating, PEG conjugating on the nanoparticle surface, we can conjugate folic acid and MTCP as well, which improve the nanoparticle and photosensitizer’s tumor accumulation. The cell TEM confirms the cellular uptake of LaF3@Au-PEG-FA/MTCP. This model has promising potential to overcome the limitation of penetration, so that the treatment procedures are done in a noninvasive way which elevates the patient’s treatment quality greatly.