Yttrium-90-doped metal–organic frameworks (MOFs) for low-dose rate internal radiation therapy of tumors

Abstract

Brachytherapy, or internal radiation therapy, is a highly effective treatment option for localized tumors. Herein, injectable and biodegradable metal–organic frameworks (MOFs) were engineered to deliver the therapeutic radioisotope yttrium-90 (⁹⁰Y). Particles of bimetallic MIL-100(Fe,Y) and Y-BTC, doped with ⁹⁰Y and ⁸⁸Y, were synthesized in a single step and retained radioyttrium in various buffer solutions. Tumor injectability and radioisotope retention were evaluated using tumor-bearing mice. In vivo analysis and calculations showed that radiolabeled MIL-100(Fe,Y) emitted more than 38% of its radioactivity, while Y-BTC emitted greater than 75% of its radioactivity, for 7 days at the tumor site upon intratumoral injection, without significant yttrium accumulation in off-target tissues. The anticancer effects of MIL-100(Fe,Y,⁹⁰Y) and ⁹⁰Y,Y-BTC particles were assessed using 3D multicellular tumor spheroids and a tumor-bearing mouse model, respectively. ⁹⁰Y-doped MIL-100(Fe,Y) particles penetrated A549 tumor spheroids and caused superior cytotoxic effects compared to non-radioactive particles or ⁹⁰YCl₃, added at the same dose. Brachytherapy with ⁹⁰Y-doped Y-BTC MOFs induced inhibition of B16F1 melanoma tumor growth and resulted in an increased median survival of 8.5 days compared to 4.5 days in untreated mice. This study shows the feasibility of preparing radioactive ⁹⁰Y-containing biodegradable non-toxic MOF particles that are advantageous for low-dose rate internal radiotherapy.