| 摘要: | 目前全世界正進入精確和個性化醫學的時代，根據每個患者的需求量身定製藥物，然後將藥物選擇性的遞送給病灶處,但不傷害健康的細胞。在癌症治療中，為達到精準治療的有效策略是依據腫瘤細胞特定的酵素，將治療劑或顯像劑與標靶基質連接來設計前驅藥物，前驅藥物將可以選擇性水解在病理細胞。葡萄醣醛酸?(β-glucuronidase, βG)是重要的腫瘤標記。因腫瘤處具有較高的βG活性，開發可同時被葡萄醣醛酸?(-glucuronidase, G)調控(off/on)之治療/照影雙功能前驅藥物Glu-NIRoff-Prodrug，利用抗腫瘤藥物的發色團, 應用photo-induce proton transfer(PET)原理焠熄近紅外光訊號，使治療/照影雙功能前驅藥物Glu-NIRoff-Prodrug具有低背景的優勢，表現出微不足道的細胞毒性和非常弱的螢光，在G專一性活化後, 前驅藥物由分子釋出有活性的抗腫瘤藥物, 也失去質子轉移焠熄近紅光訊號的作用, 才可再散發近紅外光訊號。因此，可用於標靶策略的腫瘤治療和即時偵測活體內腫瘤G活性，以便即時造影評估葡萄糖酸?前驅抗癌藥物的治療效果。創新開發同時治療和照影的前驅藥物, 可作為癌症的精確診斷和標靶治療。
The world is now entering the era of precision and personalized medicine, where drugs will be tailored for each patient’s needs and then delivered specifically to diseased but not normal cells. In cancer treatment. One attractive strategy for achieving the desired pathologic cell is prodrug. The prodrug specificity is to link an established therapeutic or imaging agent to a targeting substrate, it can hydrolysis selectively in the pathologic cell. Beta-glucuronidase (G) is a tumor biomarker. Because of the high βG activity at the tumor site, its potential biomarker for cancer diagnosis and prodrug therapy. Development theranostics (Glu-NIRoff-Prodrug) via G off/on that combining cancer precision diagnosis and targeted therapy. Antitumor drugs as chromophore, using photo-induce proton transfer (PET) principle to quench near-infrared light signals. Thus, Glu-NIRoff-Prodrug has the advantage of a low background, shows negligible cytotoxicity and very weak fluorescence. After G specific activation, Glu-NIRoff-Prodrug release active antitumor drugs from molecule, it also loses the role of proton transfer to quench the near red light signal, then the near infrared light signal be emitted. Therefore, Glu-NIRoff-Prodrug can be used for target tumor treatment and real-time detection of tumor G activity in vivo. Immediate angiography to evaluate the therapeutic effect of glucuronide anticancer drugs. Innovative development of Glu-NIRoff-Prodrug that simultaneously treat and illuminate, can be used as a precise diagnosis and target treatment for cancer. |
