Liu Shuang, Wen Mei, Huang Mengmeng, Wang Haifeng, Chen Zhigang, Yu Nuo
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai 201620, China.
J Colloid Interface Sci. 2022 Jun 15;616:23-33. doi: 10.1016/j.jcis.2022.02.040. Epub 2022 Feb 12.
Nanoscale metal-organic frameworks composed of heavy metal ions (such as Fe and Cu) as metal nodes have been utilized for cancer therapy, but they suffer from serious quenching in fluorescence and photo-sono sensitization due to their paramagnetism and unsaturated 3d orbitals. To solve these problems, we synthesize nanoscale hematoporphrin-based frameworks with Al ions as metal nodes (AlHFs) rather than heavy metals and achieve enhanced photo-sono therapy of malignant tumors. The hydrophilic AlHFs are prepared by first assembling hematoporphrin molecules and Al(III) trimers via covalent coordination and then surface-modifying them with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(polyethylene glycol) (DSPE-PEG) molecules. Under excitation with 660 nm light or ultrasound, AlHFs-PEG can produce 3.6-fold or 2.8-fold more O species than the as-synthesized nanoscale Fe-hematoporphrin frameworks (FeHFs) because the Al ions without 3d orbitals are not beneficial for energy transfer, while Fe ions with unsaturated 3d orbitals and paramagnetism can cause significant energy transfer. AlHFs-PEG exhibits high biocompatibility and can be engulfed by cells to produce intracellular O for efficient destruction of cells. With the high biosafety and the photo-sono sensitization, the growth rate of tumors in mice with the AlHFs-PEG injection is significantly inhibited upon exposure to both light and ultrasound, showing higher therapeutic efficacy than photodynamic therapy or sonodynamic therapy alone. Therefore, the present work not only presents the preparation of AlHFs-PEG for tumor photo-sono therapy but also provides some insights for developing nanoscale frameworks with light metal ions as metal nodes.
由重金属离子（如铁和铜）作为金属节点组成的纳米级金属有机框架已被用于癌症治疗，但由于其顺磁性和不饱和3d轨道，它们在荧光和光声敏化方面存在严重的淬灭现象。为了解决这些问题，我们合成了以铝离子作为金属节点的纳米级血卟啉基框架（AlHFs）而非重金属，并实现了对恶性肿瘤的增强光声治疗。亲水性AlHFs的制备方法是，首先通过共价配位组装血卟啉分子和铝（III）三聚体，然后用1,2 - 二硬脂酰 - sn - 甘油 - 3 - 磷酸乙醇胺 - N -（聚乙二醇）（DSPE - PEG）分子对其进行表面改性。在660 nm光或超声激发下，AlHFs - PEG产生的氧物种比合成的纳米级铁 - 血卟啉框架（FeHFs）多3.6倍或2.8倍，因为没有3d轨道的铝离子不利于能量转移，而具有不饱和3d轨道和顺磁性的铁离子会导致显著的能量转移。AlHFs - PEG表现出高生物相容性，可被细胞吞噬以产生细胞内氧从而有效破坏细胞。凭借高生物安全性和光声敏化作用，注射AlHFs - PEG的小鼠肿瘤在光照和超声作用下生长速率显著受到抑制，显示出比单独的光动力疗法或声动力疗法更高的治疗效果。因此，本工作不仅展示了用于肿瘤光声治疗的AlHFs - PEG的制备，还为开发以轻金属离子作为金属节点的纳米级框架提供了一些见解。
