Size-Controlled Synthesis of Drug Loaded Zeolitic Imidazolate Framework in Aqueous Solution and Size Impact on Their Cancer Theranostics In Vivo.

Recently, metal-organic frameworks (MOFs) have shown great potential for drug delivery, yet little has been done to study how particle size impacts their tumor targeting and other in vivo features. This plight is probably due to two challenges: 1) lack of a biocompatible method to precisely control the size of drug loaded MOFs; 2) lack of a robust and facile radiolabeling technique to trace particles in vivo. Here, we report a one-pot, rapid and completely aqueous approach that can precisely tune the size of drug loaded MOF at room temperature. A chelator free 64Cu-labeled method was developed by taking the advantage of this rapid and aqueous synthesis. Cancer cells were found to take drug loaded MOFs in a size-dependent manner. The in vivo biodistribution of drug loaded MOF was analyzed with PET imaging, which as far as we know was the first time to quantitatively evaluate MOF in living animals, unveiling that 60 nm MOF gave longer blood circulation and over 50% higher tumor accumulation than 130 nm MOF. In all, this size-controlled method helps to find the optimal size of MOF as a drug carrier and opens new possibilities to construct multifunctional delivery systems for cancer theranostics.