Formulation of Metal–Organic Framework-Based Drug Carriers by Controlled Coordination of Methoxy PEG Phosphate: Boosting Colloidal Stability and Redispersibility

Abstract

Metal−organic framework nanoparticles (nanoMOFs) have been widely studied in biomedical applications. Although substantial efforts have been devoted to the development of biocompatible approaches, the requirement of tedious synthetic steps, toxic reagents, and limitations on the shelf life of nanoparticles in solution are still significant barriers to their translation to clinical use. In this work, we propose a new postsynthetic modification of nanoMOFs with phosphate-functionalized methoxy polyethylene glycol (mPEG− PO 3 ) groups which, when combined with lyophilization, leads to the formation of redispersible solid materials. This approach can serve as a facile and general formulation method for the storage of bare or drugloaded nanoMOFs. The obtained PEGylated nanoMOFs show stable hydrodynamic diameters, improved colloidal stability, and delayed drug-release kinetics compared to their parent nanoMOFs. Ex situ characterization and computational studies reveal that PEGylation of PCN-222 proceeds in a two-step fashion. Most importantly, the lyophilized, PEGylated nanoMOFs can be completely redispersed in water, avoiding common aggregation issues that have limited the use of MOFs in the biomedical field to the wet forma critical limitation for their translation to clinical use as these materials can now be stored as dried samples. The in vitro performance of the addition of mPEG−PO 3 was confirmed by the improved intracellular stability and delayed drug-release capability, including lower cytotoxicity compared with that of the bare nanoMOFs. Furthermore, z-stack confocal microscopy images reveal the colocalization of bare and PEGylated nanoMOFs. This research highlights a facile PEGylation method with mPEG−PO 3 , providing new insights into the design of promising nanocarriers for drug delivery.

Facile synthesis of superparamagnetic nickel-doped iron oxide nanoparticles as high-performance T1 contrast agents for magnetic resonance imaging

“…The phosphate group can form very strong M–O–P coordination bonds with metals. 30,34 As an ideal anchor group, the ligand containing phosphate group can replace the hydrophobic coatings and irreversibly bind to inorganic nanoparticles, forming a dense monolayer on the surface of the nanoparticles. Polyethylene glycol (PEG) is a linear water-soluble polymer, which can effectively avoid recognition and phagocytosis of the reticuloendothelial system and prolong the retention time in the blood circulation.…”

The uptake of metal–organic frameworks: a journey into the cell

“…Chen et al developed MOF coatings for a series of Zr-based MOFs (PCN-128, 222, NU-901, MOF-808, UiO-66) to protect MOFs from the phosphate-ion degradation. 103 In this case, the coordination to the metal cluster was done through a phosphate head connected to a PEG chain (mPEG-PO 3 ). The phosphate head provided stronger binding than previous designs based on e.g.…”

Precision Synthesis of Conjugated Polymers Using the Kumada Methodology

“…While aliphatic side chains enable solubility in organic solvents, side chains that enable the solubility of conjugated polymers in polar or aqueous solutions are in high demand. Oligo- and poly­(ethylene glycol) (OEG and PEG) are frequently used examples of solubilizing side chains with the added benefit of also facilitating electron and ion transport, preventing nonselective binding, − and acting as a polarity contrast agent in self-assembly. − The McCullough group reported the chain-growth synthesis of 3-alkoxythiophenes, where the side chains consisted of OEG, and noted superior electrical conductivities and stabilities under ambient conditions upon doping compared to their P3AT analogues . The drawback is that OEG and other polar side chains are hygroscopic, which is directly opposed to the strict water-free conditions required for controlled KCTP.…”