Lanthanide-based metal–organic frameworks solidified by gelatin-methacryloyl hydrogels for improving the accuracy of localization and excision of small pulmonary nodules

Abstract

The localization of invisible and impalpable small pulmonary nodules has become an important concern during surgery, since current widely used techniques for localization have a number of limitations, such as invasive features of hookwires and microcoils, and rapid diffusion after injection of indocyanine green (ICG). Lanthanide-based metal–organic frameworks (MOFs) have been proven as potential fluorescent agents because of their prominent luminescent characteristics, including large Stokes shifts, high quantum yields, long decay lifetimes, and undisturbed emissive energies. In addition, lanthanides, such as Eu, can efficiently absorb X-rays for CT imaging. In this study, we synthesized Eu-UiO-67-bpy (UiO = University of Oslo, bpy = 2,2'-bipyridyl) as a fluorescent dye with a gelatin-methacryloyl (GelMA) hydrogel as a liquid carrier. The prepared complex exhibits constant fluorescence emission owing to the luminescent characteristics of Eu and the stable structure of UiO-67-bpy with restricted fluorescence diffusion attributed to the photocured GelMA. Furthermore, the hydrogel provides stiffness to make the injection site tactile and improve the accuracy of localization and excision. Finally, our complex enables fluorescence-CT dual-modal imaging of the localization site.

Biomedically-relevant metal organic framework-hydrogel composites

“…Recently, the Eu-UiO-67-bpy MOF (bpy = 2,2'-bipyridyl) was used as a fluorescent dye embedded within a gelatin methacryolyl (GelMA) hydrogel matrix to improve the localisation of pulmonary nodules (Figure 12). 98 These nodules are small lesions (diameters < 1 cm) are related to early-stage lung cancer, and thus are receiving interest for early diagnosis. 136 However, these nodules are often invisible during surgery, making their localisation challenging, and existing preoperative tumour marking techniques (e.g.…”

Advances in metal–organic framework-based hydrogel materials: preparation, properties and applications

“…In the field of low-dose computed tomography (CT), Wang et al incorporated the properties of Eu-MOF and gelatin-methacryloyl to prepare a Eu-MOF/GelMA hydrogel, which was mainly used to improve the localization of small pulmonary nodules. 376 The absorption of X-rays by Eu element and luminescence properties of La-MOF were the key factors of CT imaging. A series of in vivo and in vitro experiments were used to verify the applicability of the system.…”

Engineering of Metal–Organic Frameworks/Gelatin Hydrogel Composites Mediated by the Coacervation Process for the Capture of Acetic Acid

“…37 It should be noted that MOFs based on divalent cations (ZIF-8, ZIF-67, and HKUST) were mainly used for the processing of gelatin-based hydrogels while interfacing gelatin with MOFs of higher chemical stability such as the series of UiO-66(Zr) was only rarely described. 33 Therefore, the processing of MOF/gelatin hydrogel with a high porosity, high chemical stability, and high MOF content would be most desirable to further optimize their performance. Herein, the thermo-reversible character of gelatin associated to a liquid− liquid phase separation process, that is, coacervation, 38,39 was exploited to prepare a series of gelatin/UiO-66-X (X = H, CF 3 , and NH 2 ) and gelatin/MOF-801 composites that combine attractive features such as high MOF loading (>80 wt %), large porosity, homogeneous MOF distribution in the host matrix, and a tunable hydrophobic−hydrophilic balance.…”

“…Such ability of gelatin for morphogenesis in soft conditions was mainly ascribed to its self-organization properties into triple helices and the existence of attractive interactions at the fluoroapatite/gelatin interface. Recently, the synthesis of MOF–gelatin hydrogels was mainly reported for bioapplications related to tissue engineering, wound healing, drug delivery, or bioimaging. − These composites were mainly prepared through the impregnation of preformed MOF particles into functionalized gelatin-based scaffolds or hybrid hydrogels or the physical gelation of gelatin in the presence of MOF particles eventually associated to electrospinning. − Although these hydrogels present interesting performance, the large majority of these composites suffers from a low porosity as a result of the very low amount of MOF (<10 wt %) and this strongly limits the exploitation of their physico-chemical properties and drug delivery properties. − A MOF–gelatin composite was also used for water purification with however a low MOF content and/or a low porosity . It should be noted that MOFs based on divalent cations (ZIF-8, ZIF-67, and HKUST) were mainly used for the processing of gelatin-based hydrogels while interfacing gelatin with MOFs of higher chemical stability such as the series of UiO-66­(Zr) was only rarely described .…”