Efficient drug delivery of 5-fluorouracil by a biocompatible Zn-metal-organic framework nanostructure and anti-liver cancer activity study

Song, BH; Ding, X; Zhang, ZF; An, GF

Abstract

Porous metal-organic frameworks (MOFs) are structures made up of inorganic nodes and organic ligands, which can be used as crystalline vessels to accommodate various functional guests. This study reports on the drug delivery of a new porous metal-organic framework [Zn-3(BTC)(2)(Aml)(H2O)(2)](MeOH)(6) (1, H3BTC = 1,3,5-benzenetricarboxylic acid, Aml = ammeline). The Zn-MOF nanocomposites were synthesized by reaction of Zn(NO3)(2)center dot 6H(2)O and the organic ligand with the aid of polyvinyl pyrrolidone. Stability and porosity of this nanostructure have been confirmed via the PXRD measurement and gas sorption studies. Due to its large BET surface areas, suitable window size, and high density of open free N sites, this MOF has been used for the anticancer drug 5-fluorouracil (5-Fu) storage/delivery, a moderate-high 5-Fu loading capacity, and pH-dependent drug release behavior which could be observed. Furthermore, the in vitro cytotoxicity of the nano-1 and the 5-Fu@nano-1 composite toward the human normal fibroblastic epithelial cell line (HFL1) and human liver cancer cell line HepG2 has been evaluated via the MTT assay.

Keywords: Metal-organic framework; Nanostructure; 5-Fu delivery; Biocompatibility; MTT assay

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Zinc-Based MOFs (Zn-MOF)

Zn-metal-organic frameworks (Zn-MOFs) are emerging as promising materials in the field of drug delivery due to their unique properties. Composed of zinc ions coordinated with organic ligands, Zn-MOFs offer high surface area, tunable porosity, and biocompatibility, making them ideal for loading and releasing therapeutic agents. Their porous structure allows for the encapsulation of a wide variety of drugs, including small molecules, proteins, and nucleic acids. The controlled release of drugs from Zn-MOFs can be achieved through pH-responsive or enzyme-sensitive mechanisms, which enhance the targeting and efficacy of treatments while minimizing side effects. Furthermore, the versatility in functionalizing the surface of Zn-MOFs enables targeted delivery to specific tissues or cells, improving the precision of treatments. Recent studies demonstrate the potential of Zn-MOFs in cancer therapy, where they facilitate the delivery of chemotherapeutic agents directly to tumor sites, thereby reducing systemic toxicity and improving therapeutic outcomes.