In Vivo Targeting and Positron Emission Tomography Imaging of Tumor with Intrinsically Radioactive Metal–Organic Frameworks Nanomaterials

Abstract

Nanoscale metal–organic frameworks (nMOF) materials represent an attractive tool for various biomedical applications. Due to the chemical versatility, enormous porosity, and tunable degradability of nMOFs, they have been adopted as carriers for delivery of imaging and/or therapeutic cargos. However, the relatively low stability of most nMOFs has limited practical in vivo applications. Here we report the production and characterization of an intrinsically radioactive UiO-66 nMOF (89Zr-UiO-66) with incorporation of positron-emitting isotope zirconium-89 (89Zr). 89Zr-UiO-66 was further functionalized with pyrene-derived polyethylene glycol (Py–PGA-PEG) and conjugated with a peptide ligand (F3) to nucleolin for targeting of triple-negative breast tumors. Doxorubicin (DOX) was loaded onto UiO-66 with a relatively high loading capacity (1 mg DOX/mg UiO-66) and served as both a therapeutic cargo and a fluorescence visualizer in this study. Functionalized 89Zr-UiO-66 demonstrated strong radiochemical and material stability in different biological media. Based on the findings from cellular targeting and in vivo positron emission tomography (PET) imaging, we can conclude that 89Zr-UiO-66/Py–PGA-PEG-F3 can serve as an image-guidable, tumor-selective cargo delivery nanoplatform. In addition, toxicity evaluation confirmed that properly PEGylated UiO-66 did not impose acute or chronic toxicity to the test subjects. With selective targeting of nucleolin on both tumor vasculature and tumor cells, this intrinsically radioactive nMOF can find broad application in cancer theranostics.

Radiolabeled Nanoparticles in Nuclear Oncology

“…These octahedron-shaped nanocarriers were labeled with 89 Zr, decorated with pyrene-derived polyethylene glycol (Py-PGA-PEG) chains, actively targeted with F3 ligand and loaded with DOX. The results were encouraging as there was no toxicity referred to the experimental murine models [38]. A chelator-free system of radiolabeled mesoporous silica nanoparticles (MSN) was presented attaining a long-term in vivo stability of more than 20 days.…”

“…Therefore, these nanoconstructs could unambiguously be considered as a useful tool in RES theranostics [92]. [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]2018 organs, while in the case of oral administration low-dose distribution to most organs was confirmed, indicating absorption of the nanoconstructs [93].…”

Metal–Organic Frameworks in Modern Physics: Highlights and Perspectives

“…[127] Metabolites doped with β + -radioactive isotopes like 18 F, 11 C, 13 N, 15 O, act as molecular probes for the location of tumors, and the study of artery diseases and other pathologies. [128] [128] …”

“…Sci. [128] modern materials. a) Illustration of MOF structure with a central paramagnetic ion as a clock qubit.…”

Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal–organic frameworks nanoparticles on breast cancer

“…One of these safe multipurpose nanomaterials could be metal–organic frameworks (MOFs). MOFs formed by various of metal ion nodes coordinated to organic molecule linkers have exhibited great potentials as drug nanocarriers due to their high pore volume, large surface area, and easy modulation of pore sizes via tuning of organic groups within the frameworks (Chen et al, ; Sun et al, ). The zeolitic imidazolate framework (ZIF‐8), in particular, is a nontoxic and biocompatible MOFs consisting of zinc ions and 2‐methyl imidazolate.…”