Nanoparticles based on MIL-101 metal-organic frameworks as efficient carriers of therapeutic 188Re radionuclide for nuclear medicine

Nuclear medicine presents one of the most promising modalities for efficient non-invasive treatment of a variety of cancers, but the application of radionuclides in cancer therapy and diagnostics is severely limited by their nonspecific tissue accumulation and poor biocompatibility. Here, we explore the use of nanosized metal-organic frameworks (MOFs) as carriers of radionuclides to order to improve their delivery to tumour. To demonstrate the concept, we prepared polymer-coated MIL-101(Cr)-NH2MOFs and conjugated them with clinically utilized radionuclide188Re. The nanoparticles demonstrated high loading efficacy of radionuclide reaching specific activity of 49 MBq mg-1. Pharmacokinetics of loaded MOFs was investigated in mice bearing colon adenocarcinoma. The biological half-life of the radionuclide in blood was (20.9 ± 1.3) h, and nanoparticles enabled it to passively accumulate and retain in the tumour. The radionuclide delivery with MOFs led to a significant decrease of radioactivity uptake by the thyroid gland and stomach as compared with perrhenate salt injection, which is beneficial for reducing the side toxicity of nuclear therapy. The reported data on the functionalization and pharmacokinetics of MIL-101(Cr)-NH2for radionuclide delivery unveils the promising potential of these MOFs for nuclear medicine.