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

Abstract

Recently, metal−organic frameworks (MOFs) or coordination polymers have shown great potential for drug delivery, yet little has been done to study how particle size affects their tumor targeting and other in vivo features. This plight is probably due to two challenges: (1) the lack of a biocompatible method to precisely control the size of drugloaded MOFs and (2) the 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 64 Cu-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 drugloaded MOF was analyzed with positron emission tomography imaging, which, as far as we know, was used for the first time to quantitatively evaluate MOF in living animals, unveiling that 60 nm MOF showed longer blood circulation and over 50% higher tumor accumulation than 130 nm MOF. Altogether, 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.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

“…Therefore, the anti-cancer ability of DOX@Azif-8 with different particle sizes is: 30 nm > 60 nm > 90 nm > 130 nm. 60 Stimulus-responsive drug delivery systems are receiving increasing attention because they can receive a stimulus to release a higher concentration of drugs in a specic target site while producing a smaller impact on other parts of the body. Acceptable stimuli include internal variables (pH and glutathione (GSH)) and external stimuli (light, heat, and magnetic eld).…”

Metal Organic Frameworks as Drug Targeting Delivery Vehicles in the Treatment of Cancer

“…TCPP@PCN-24 with a particle size of 90 nm has the best photodynamic therapy effect, and TCPP@PCN-24 with a particle size of 190nm has the worst effect. Duan also proved that 60nm AZIF-8 has better anti-tumor effect than other particle sizes, due to the strongest retention effect in the tumor area of this particle size [37].…”

“…Therefore, it is necessary to control the particle size of MOFs. In a typical example, Duan et al devoted research to controlling the particle size of AZIF-8 (amorphous zeolitic imidazolate framework-8) by a simple method and studying the effects of its particle size on the treatment of tumors [37]. They used nontoxic poly-allylamine hydrochloride (PAH) to precisely control the size of the AZIF-8 by one-pot synthesis method, which broke the tradition of being unable to control the MOFs' particle size precisely and the need for toxic solvents for synthesis and modification.…”

Versatile Nanoscale Metal–Organic Frameworks (nMOFs): An Emerging 3D Nanoplatform for Drug Delivery and Therapeutic Applications

“…[ 30a ] Similarly, Liu and coworkers employed nontoxic poly(allylamine hydrochloride) to precisely modulate the size of monodispersed ZIF‐8 (30–150 nm) under aqueous environment. [ 32 ] This water‐soluble cationic polymer could compete with the imidazole ligands to coordinate zinc ions, which contributed to slowing down the nucleation rate and accordingly yielding larger particles.…”