4.8 Article

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy using CaCO3 Mineralized Metal-Organic Framework

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 40, Pages 14134-14139

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201907388

Keywords

antitumor reagents; drug delivery; drug design; metal-organic frameworks; nanostructures

Funding

  1. National Natural Science Foundation of China [21535004, 91753111, 21874086, 21775094]
  2. Key Research and Development Program of Shandong Province [2018YFJH0502]

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Dihydroartemisinin (DHA) has attracted increasing attention as an anticancer agent. However, using DHA to treat cancer usually depends on the synergistic effects of exogenous components, and the loss of DHA during delivery reduces its effectiveness in cancer therapy. Reported herein is a programmed release nanoplatform of DHA to synergistically treat cancer with a Fe-TCPP [(4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid)] NMOF (nanoscale MOF) having a CaCO3 mineralized coating, which prevents DHA leakage during transport in the bloodstream. When the nanoplatform arrives at the tumor site, the weakly acidic microenvironment and high concentration of glutathione (GSH) trigger DHA release and TCPP activation, enabling the synergistic Fe2+-DHA-mediated chemodynamic therapy, Ca2+-DHA-mediated oncosis therapy, and TCPP-mediated photodynamic therapy. In vivo experiments demonstrated that the nanoplatform showed enhanced anticancer efficiency and negligible toxicity.

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