開發多功能性磁性奈米粒子用於胰臟癌的早期診斷

Abstract

本文研究的目的為設計功能性的磁性奈米粒子應用於光學與磁振造影雙功能的對比劑，而我們將利用MnMEIO-NH2-mPEG同樣修飾上MUC4之抗體，作為偵測胰臟癌細胞表面上的MUC4蛋白。本文研究奈中已經成功設計新型的高分子聚合物mPEG-NH2-silane修飾到奈米粒子表面，其共軛胺基會在奈米內側形成而不會裸露在外，此時會降低非特異性的吸附或是鍵結，然而為了讓奈米粒子更接近電中性，利用半胱胺酸遮蔽內側胺基，使電性中和。動態光散射儀顯示，MnMEIO鍵結MUC4抗體可使水合直徑由39.3 ± 2.2 nm 增加至 55.9 ± 5.6 nm。MnMEIO-Ab-Cy777-mPEG在20 MHz， 37.0 ± 0.1 ℃下的r1及r2弛緩率分別為 35.7 ± 1.5 和 216.1 ± 4.4 mM-1S-1，在MRI體外顯影上針對表面MUC4蛋白之細胞株獲得很好的對比影像。因此，本文研究已成功設計出用於胰臟癌的高度專一性的功能性磁性奈米粒子，可用於胰臟癌的早期診斷。

Novel aspect of nanotechnology and biotechnology has been extensively exploited to develop multimodal contrast agent for cancer detection. We have developed highly specific dual modality T2 weighted MR-optical imaging agents (MnMEIO-antiMUC4-Cy777-mPEG NPs) for early detection of pancreatic cancer. A novel PEG derivative, methoxypoly(ethylene glycol)-ethylamine-silane (mPEG-NH2-silane), was strategically designed and synthesized such that amine group of NPs remain buried deep inside the entangled mPEG chains. Furthermore, in order to achieve nearly neutral surface charge of MnMEIO NPs, nonconjugated passively masked NH2 was further blocked by cysteine. Dynamic light-scattering (DLS) measurements revealed that the mPEG-NH2-silane coated MnMEIO NPs has a relatively narrow size distribution with mean size of 39.3 ± 2.2 nm which was increased 55.9 ± 5.6 nm upon conjugating anti-MUC4 mAb, and Cy777. The relaxivity values (r1 and r2) of the MnMEIO-Ab-Cy777-mPEG NPs measured at 20 MHz and 37.0 ± 0.1 牵C are 35.7 ± 1.5 and 216.1 ± 4.4 mM-1s-1, respectively. In vitro MR image shows significant contrast enhancement in MUC4 positive cell line. Therefore, we believe the highly sensitive and specific MnMEIO-antiMUC4-Cy777 NPs introduced in the present thesis could potentially be used for early detection of pancreatic cancer.