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A targeted nanoparticle delivers a one-two punch to tumors

Wenbin Lin, Ludwig Cancer Research Chicago
Wenbin Lin

Nanoscale metal organic frameworks (nMOFs)—a versatile class of nanomaterials made by linking metal ions with organic molecules to create porous, crystalline structures—can be constructed to carry drugs and unload them into tumors in response to selected triggers. Ludwig Chicago’s Wenbin Lin and colleagues reported in an August paper in the Journal of the American Chemical Society a heavy metal–based nMOF that both delivers a cancer drug and amplifies the effects of radiotherapy through the enhanced deposition of energy and generation of reactive oxygen species (ROS). The nMOF designed by Wenbin and his colleagues consists of a dozen atoms of the metal hafnium linked by organic molecules to which a prodrug of SN38 is covalently attached. Upon irradiation, the nMOF’s electron-rich hafnium atoms serve as radiosensitizers, causing the generation of large quantities of hydroxyl radicals. Aside from killing cancer cells, these free radicals react with the nMOF to trigger the release of SN38—the active metabolite of the cancer drug irinotecan. This permits the targeted, synergistic treatment of tumors with radio- and chemotherapy and reduces the dosage of radiation required for effective treatment. Wenbin and his team showed that an intratumoral injection of nanoparticles followed by radiotherapy efficiently inhibits tumor growth in mouse models of colon and breast cancer.

Nanoscale metal–organic framework with an X-ray triggerable prodrug for synergistic radiotherapy and chemotherapy
Journal of the American Chemical Society, 2023 August 15

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