磁性奈米粒子穿透薄膜層之傳輸機制研究

Abstract

磁性粒子因其優異之生物相容性，亦已被考慮應用於生物醫學技術上，其方 向可約略分為以下二大類: 細胞感受器標靶(Targeting to cell receptor)與精確 細胞吸收效果(Targeted cell uptake) 。細胞感受器標靶(Targeting to cell receptor) 乃基於磁性粒子之奈米級尺寸小於典型細胞(~10~100μm) ，且與一般之基因 及蛋白質相當，故而可於磁性粒子表面披覆(coating)生物標識器(如抗體及藥 物) ，並可利用外部磁場導引至目標組織或細胞區域，而與組織或細胞感受 器(cell receptor)結合併附著於細胞表面。利用此一磁性粒子附著細胞表面之技 術，則可有效應用於精準釋藥之治療過程或細胞標籤化(cell labeling)應用，而 細胞標籤化功能亦可再配合外部磁場進而進行細胞分類。精確細胞吸收效果 (Targeted cell uptake)須要磁性粒子直接進入細胞或組織內，稱之為細胞吸收 (cell uptake) 。此應用常發生於欲利用磁性粒子加強腫瘤細胞於核磁共震顯影 技術(MRI)下之影像對比強度，或利用腫瘤細胞內磁性粒子於高蘋頻率交流電 磁場，受激發產生熱度，而破壞腫瘤細胞之熱療法(hyperthermia) ，以及藉由 磁性粒子表面披覆生物單元(如基因)，直接進入細胞進行治療(如基因治療 法)。 除以上直接使用磁性粒子之生物醫學技術應用情況外，於一般化工或藥理應 用，亦常有希望特定物質通過可滲透性薄膜層之情形(如希望美容用真珠粉可 有效穿越皮膚表層而進入皮下組織)，而未來此類應用亦可比照上述情況，將 此特定物質結合磁性粒子，利用外部磁場來操控其傳輸運動，故而對磁性粒 子通過特定薄膜層之力學機制研究，深具研究價值。 本提案計畫為全期三年之計畫，預計以三年時程完成三階段之研究進度，其 主要研究目的為研究於不同磁場條件下，奈米磁性粒子通過具滲透性薄膜層 之力學機制，並建立實用之數學模式，並針對此研究同時進行實驗與數值模 擬。第一年將針對磁性粒子之基本運動模式進行探討，並建製基本之實驗機 構，進行相對應之實驗以驗證或獲取數值模擬所須之各項物理性質或參數。 第二年則針對生醫相容之含有奈米磁性粒子之穩定水基磁性流體及未經處理 之奈米磁性粒子穿透均質滲透性薄膜層(PU 人工膜、生物皮膚表層等)進行模 擬及實驗。第三年則進行含有生醫相容之奈米磁性粒子之穩定水基磁性流體 及未經處理之奈米磁性粒子穿透複合性滲透性薄膜層(生物皮膚表層組織及 細胞等)之模擬及實驗。

Magnetic nanoparticles have long been advocated for biomedical applications because of their excellent bio-compatible and superparamagnetic behaviors. In the future biomedical applications, there are two possible directions: (1) targeting to cell receptors and (2) targeted cell uptake. For the targeting to cell receptors, if nanoparticles were conjugated with groups and able to permit specific recognition of cell types, more precise cell selections will be able to achieved. Furthermore, accurate drug delivery can also be accomplished if the particles can be targeted to the malfunctional cell receptor, such as tumors. On the other hand, targeted cell uptake requires the capture and internalization of the nanoparticles by the cell. These cell uptake behaviors are necessary for the several biomedical applications, such as enhancements of MRI contrast, hyperthermic treatments and gene therapies. For both situations described above, the nanoparticles usually need to cross through permeable membranes and layers. In addition, problems of similar particles transportation through permeable membranes are encountered in the fields of chemical engineering and mass filtrations. As a result, the transport mechanism of nanoparticles through permeable membranes and layers is a subject worthy to explore thoroughly. The present proposal aims to investigate the transportation of magnetic nanoparticles crossing a permeable membrane or layer under the presence of magnetic fields, in a three-year period. The first-year sub-project focuses mainly on the establishment of fundamental theoretical models and experimental apparatus. Basic experiments dealing with simple membranes or layers, such as a PU membrane which its physical properties are already available, will be carried to either compare or validate the theoretical studies. The effects of various parameters, i.e. field strengths, field distributions, will be investigated numerically and experimentally. In the sub-project of year two, the main goal will be to conduct more practical experiments, such as particles crossing a single layer of animal (or artificial) skin. In this situation, the single skin layer is considered as a medium with homogeneous permeability. Again, the relevant parameters will be analyzed systematically. In the final third year, the attentions will be turned to a more realistic situation of a composite layer, i.e. the animal (or artificial) skin containing multiple layers or 3 cell-layer round window membrane of ears. To simulate these situations, the distributions of permeability of the layers will be considered as hetero-homogeneous. Detailed understandings regarding the transport mechanism of nanoparticles through permeable layers under the presence of magnetic field as well as useful mathematical models are expected to be accomplished after the full execution of this three-year proposed project.