Surface defection reduces cytotoxicity of Zn(2-methylimidazole)₂ (ZIF-8) without compromising its drug delivery capacity

Abstract

Zn(2-methylimidazole)2 (ZIF-8), as one of the most important metal-organic framework (MOF) molecules, is a promising candidate for drug delivery due to its low-density structure, high surface area, and tunable frameworks. However, ZIF-8 exhibits a high cytotoxicity associated with its external hydrophobic surface, which significantly restricts its application in drug delivery and other biomedical applications. Commonly used chemical functionalization methods would convert the hydrophobic surface of ZIF-8 to hydrophilic, but the generated functional groups on its internal surface may reduce its pore sizes or even block its pores. Herein, a surface defection strategy was applied on the external surface of ZIF-8 to enhance its hydrophilicity without reducing or blocking the internal pores. In this approach, mechanical ball-milling was used to incur defects on the external surface of ZIF-8, leading to unsaturated Zn-sites and N-sites which subsequently bound H2O molecules in an aqueous environment. Furthermore, hydroxyurea delivery and cell cytotoxicity of ZIF-8 with and without the external surface treatment were evaluated. It was found that 5-min ball milling changed the hydrophobic–hydrophilic balance of ZIF-8, resulting in significantly higher cell viability without compromising its hydroxyurea loading and release capacity. Such a simple mechanical ball-milling followed by water-treatment provides a general technique for surface-modification of other MOF molecules, which will undoubtedly magnify their biomedical applications.

Tuning the Catalytic Performance of Novel Composites Based on ZIF‐8 and Nafen through Dimensional and Concentration Effects in the Synthesis of Propylene Glycol Methyl Ether

“…A new band at 828 cm –1 is observed. This band can be assigned to the epoxide ring stretching , . Moreover, a new band at 426 cm –1 is observed in the region of 400–450 cm –1 as well as a characteristic band at 420 cm –1 assigned to the Zn–N mode due to the interaction between a Zn atom and an N atom of 2‐methylimidazole .…”

“…The ZIF‐8 ( 2 ) (190–260 nm) sample was prepared in aqueous media according to . Zn(CH 3 COO) 2 2H 2 O (0.549 g, 2.5 mmol) and 2‐methylimidazole (20.525 g, 250 mmol) were dissolved in water (90 mL).…”

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

“…This method will not change the structure and size of the internal pores of ZIF-8, and can ensure that the hydrophilic properties of ZIF-8 are improved without affecting its drug loading capacity and release performance. 49…”

Synthesis of Folic Acid-Modified DOX@ZIF-8 Nanoparticles for Targeted Therapy of Liver Cancer

“…Among these nanocarriers, zeolitic imidazolate framework (ZIF), a subclass of MOF, with large surface areas, high porosity, and high stability, has been extensively utilized in drug delivery. Recently, several studies showed that ZIF-8 possessed a remarkable drug loading capacity and a pH-triggered control of drug release property [10][11][12][13][14][15][16]. However, a major drawback is their lack of tumor targeting ability.…”