功能性金屬有機框架材料於雙模態光聲影像與電腦斷層掃描之應用

Abstract

非侵入式癌症影像技術能夠提供結構與功能層面的腫瘤綜合資訊，進而提升診斷準確性。本研究中，我們開發了負載鈀奈米顆粒的基於鉿金屬有機框架（Hf-EDB）材料，即 Pd@Hf-EDB，作為高效的電腦斷層掃描（CT）與光聲影像（PAI）雙模態顯影劑。Pd@Hf-EDB 的優異表現來自於三方面的協同作用：(i) 含高原子序元素鉿的MOF具備卓越的X光吸收能力；(ii) H2EDB有機配體具有特殊的π供體與π受體特性，能夠強力錨定貴金屬；(iii) 鈀奈米顆粒則因強烈的能帶間躍遷，在紫外到近紅外區域具有寬廣的吸收範圍。透過X光繞射（XRD）、掃描式電子顯微鏡（SEM）、穿透式電子顯微鏡（TEM）、動態光散射（DLS）與能量散射X光光譜（EDS）等分析技術，成功證實了Pd@Hf-EDB奈米粒子的合成。軟X光斷層掃描（SXT）結果進一步驗證了Pd@Hf-EDB能夠經由胰臟癌細胞株BxPC-3細胞的吞噬作用進入細胞。體外實驗顯示，Pd@Hf-EDB在CT成像中的表現優於傳統分子型對比劑（如Iohexol）。此外，Pd@Hf-EDB在紫外-可見-近紅外區域展現出廣泛的吸收範圍，且相較於金奈米棒（GNRs），在光聲影像方面具有更優異的性能。進一步透過活體異種移植腫瘤模型實驗，證實了Pd@Hf-EDB於腫瘤區域產生明顯的對比增強，展現其在PAI與CT影像的卓越應用潛力。

Noninvasive cancer imaging improves diagnostics by providing comprehensive information on structural and functional tumors. Herein, we explored palladium nanoparticles loaded hafnium-based metal-organic framework (Hf-EDB) i.e., Pd@Hf-EDB as an efficient dual modal contrast agent for computed tomography (CT) and photoacoustic imaging (PAI). The synergistic collaborations between (i) high-Z element Hf based MOF with superior X-rays absorbing capabilities, (ii) H2EDB linkers with special π-donation and π-acceptor characteristics capable of strongly anchoring noble metals and (iii) Pd nanoparticles with broad absorption in the UV to NIR regions due to strong interband transition; are ideal for implementation in CT and PAI. The successful synthesis of Pd@Hf-EDB nanoparticles were confirmed through morphology, crystallinity, and compositional characterizations using XRD, SEM, TEM, DLS, and EDS. Soft X-ray tomography (SXT), verified cellular uptake via phagocytosis of Pd@Hf-EDB by BxPC-3 tumor cells. In-vitro experiments revealed superior CT imaging performance of Pd@Hf-EDB over traditional molecular contrast agents like Iohexol. Broad absorption range in the UV-Vis/NIR regions and superior PAI capabilities of Pd@Hf-EDB relative to gold nanorods (GNRs) is reported. Furthermore, the in vivo xenograft model demonstrated significant contrast enhancements near the tumor highlighting the excellent PAI and CT capabilities of the synthesized Pd@Hf-EDB.