磁性核/無機殼奈米複合材料的合成、檢測與應用

在此，我們設計並合成了介孔洞二氧化矽(mSiO2)殼包覆之中空氧化錳(H-MnO)核的奈米複合材料(H-MnO@mSiO2)。表面的孔洞使環境水分子更容易擴散至氧化錳核，並藉由中空的氧化錳結構來增加與水分子接觸的表面積，最終提升核磁共振(magnetic resonance, MR)T1顯影訊號。為了使此結構有更廣泛的應用，我們將尾端修飾矽烷(silane)的磷光(phosphorescence)分子iridium complex藉由溶膠-凝膠(sol-gel)法共水解縮合於二氧化矽的骨架(framework)中。該iridium complex分子不僅提供了光學(optical)顯影的功能，另外其激發態能與氧分子作用來產生激發態的單氧分子可應用於光動力療法(photodynamic therapy, PDT)，孔洞的結構更能增加氧的進出而提升PDT效率。最後我們可以將不同性質的官能基修飾聚乙二醇(polyethylene glycol, PEG) 或葉酸(folic acid, FA)於二氧化矽的表面(outermost surface)來增加此奈米粒子在生醫上的應用性。在H-MnO@mSiO2(Ir)-PEG奈米材料中，藉由PEG的修飾除了能增加生物相容性、避免孔洞結構的塌陷外，還能避免生物體噬菌細胞的吞噬，因此提升在人體血液中循環的時間。此三合一(PDT, optical以及MR imaging)的奈米複合材料在細胞實驗成果上充分表現了他在生醫應用的淺力。為了增加顯影和傳遞藥物的專一性，我們更進一步將葉酸(FA)修飾於二氧化矽表面形成H-MnO@mSiO2(Ir)-FA奈米複合材料。並使用過量表現FA接受器(receptor)的HeLa細胞以及少量表現FA接受器的MIA PaCa-2細胞來評估此奈米複合材料專一顯影和標定(targeting)治療的可能性。細胞實驗結果顯示只有被標定的HeLa細胞有較強的MRI訊號和放光，也能藉單氧殺死被標定的細胞。此新型四合一(targeting, PDT, optical以及MR imaging)奈米複合材料只需改變表面的標定配位體(ligand)即能應用於其他生物系統，預期將開啟多功能T1顯影材料在生醫應用上的大門。

關鍵字

T1顯影劑；中空氧化錳；介孔洞二氧化矽；雙重顯影；光動力療法；專一性標定

並列摘要

Multifunctional uniform nanoparticles (NPs) composed of a hollow manganese nanocrystal core and a mesoporous silica shell (H-MnO@mSiO2) functionalized by phosphorescent iridium complex (Ir), and polyethylene glycol (PEG) or folic acid (FA) on the outermost surface have been strategically designed and synthesized. Both H-MnO@mSiO2(Ir)@PEG and H-MnO@mSiO2-FA NPs demonstrates its versatility in various applications. (1) The magnetic core provides the capability for T1 magnetic resonance (MR) imaging. (2) The iridium complex incorporated silica framework serves as both photosensitizer and luminescent chromophore. (3)The nano-channels in the mesoporous silica shell increase the free diffusion of oxygen and water permeability, enhancing photodynamic therapy (PDT) and T1 signal, respectively. Furthermore, for H-MnO@mSiO2(Ir)@PEG NPs, a biocompatible polymer (PEG), is anchored on outermost surface to maintain the pore structure, avoid protein adsorption and then bypasses the RES system in in vivo applications. On the other hand, H-MnO@mSiO2-FA NPs, is able to target at specific cells for bimodal imaging (both MR and optical) and PDT, and minimize collateral damage of non-targeted cells attributed by surface folic acid.

並列關鍵字

T1 contrast agent ； MnO ； hollow MnO ； mesoporous silica ； dual imaging ； photodynamic therapy

參考文獻

1.Caravan, P. Strategies for Increasing the Sensitivity of Gadolinium Based MRI Contrast Agents. Chem. Soc. Rev. 2006, 35, 512–523.

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3.Caravan, P.; Ellison, J. J.; McMurry, T. J. ; Lauffer, R. B. Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem. Rev. 1999, 99, 2293–2352.

4.Zhang, C. F.; Jugold, M.; Woenne, E. C.; Lammers, T.; Morgnstern, B.; Mueller, M. M.; Zentgraf, H.; Bock, M.; Eisenhut, M.; Semmler, W.; et al. Specific Targeting of Tumor Angiogenesis by RGD-Conjugated Ultrasmall Superparamagnetic Iron Oxide Particles Using a Clinical 1.5-T Magnetic Resonance Scanner. Cancer Res. 2007, 67, 1555–1562.

5.Martina, M. S.; Fortin, J. P.; Menager, C.; Clement, O.; Barratt, G.; Grabielle-Madelmont, C.; Gazeau, F.; Cabuil, V.; Lesieur, S. Generation of Superparamagnetic Liposomes Revealed as Highly Efficient MRI Contrast Agents for in Vivo Imaging. J. Am. Chem. Soc. 2005, 127, 10676–10685.

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磁性核/無機殼奈米複合材料的合成、檢測與應用

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