Assembly of responsive metal-phenolic network capsules for drug delivery

Microcapsules are a kind of semipermeable or closed containers prepared by physical and chemical methods from natural or synthetic materials. Since Messersmith reported the mussel-inspired surface chemistry for multifunctional coatings in 2007, polyphenols have been widely used in biomedical, food processing, and cosmetic fields because of their antioxidant and antibacterial properties. Metal-phenolic networks (MPN) capsules as a kind of functional polyphenol materials have been attracted attention in various fields from catalysis and separation to biomedicine, which was due to their biocompatibility, pH responsibility, and multifunctionality. Besides, MPN capsules with different functions (e.g., drug delivery, catalysis, magnetic resonance imaging, fluorescence imaging, and positron emission tomography) can be fabricated by metal ions and polyphenol ligands. Although preparation strategies of MPN capsules are convenient and different templates (e.g., mesoporous silica particles, calcium carbonate particles, polystyrene microspheres, metal-organic frameworks (MOFs) nanoparticles, drug molecular crystals, biological cells and emulsions) have been used, controllable preparation of MPN capsules are still challenging. Herein, we reported a novel strategy to construct MPN capsules exhibiting size controllable and thickness adjustable characteristics. Zeolite imidazolate framework-8 (ZIF-8) with regular morphology and variable sizes (200 nm to 1 mu m) were prepared by tuning the molecular weight or structure of poly(ethylene glycol) (PEG), which endow ZIF-8 as an ideal candidate to fabricate microcapsules. In addition, functional molecule (e.g., DOX) can be encapsulated in a one-pot synthesis into the template for cytotoxicity investigations. From the SEM, TEM and DLS data, it can be seen that the morphology of DOX@ZIF-8 NPs after co-encapsulation with DOX has been maintained. Furthermore, on mixing TA-Fe3+ clear solution with DOX@ZIF-8 particles DOX@ZIF-8@MPN particles were harvested. Template removal process could be easily achieved by dissolution of DOX@ZIF-8@MPN particles in EDTA aqueous solution. Thus the DOX@MPN capsules were fabricated with this facile strategy. Physicochemical properties (e.g., size, morphology, and thickness) of MPN capsules can be tuned by adjusting the template size and incubation time. The effect of TA and Fe3+ concentration and incubation time on the thickness and morphology of the capsules was studied systematically. The capsule thickness was tuned with the increase of TA-Fe3+ concentration, while the maximum thickness of 36.01 nm was obtained with TA and Fe3+ concentration are 23.5 and 37 mmol/L respectively. Then, the effect of incubation time on the capsules thickness was also explored, showing that the thickness of MPN capsules increased with the addition of incubation time. When the incubation time was 24 h, the thickness was 41.81 nm. MPN capsules can be assembled by the pyrogallol groups on TA with Fe3+ at pH 8.0. However, the pH sensitivity of MPN capsules could lead to capsules disassemble in acidic aqueous solution at pH 4.5. In conclusion, we reported a facile strategy to assemble MPN capsules with ZIF-8 particles as template. On co-encapsulation of a functional molecule DOX into the ZIF-8 particles, after template removal with EDTA, DOX@MPN capsules were obtained exhibiting higher toxicity to cancer cells (e.g., HeLa cells) compared with the MPN capsules. This study provides a strategy to prepare functional MPN capsules for therapeutic delivery.