Metal-organic frameworks as potential drug carriers

Abstract

Nanoparticle-based therapeutics have received increasing attention, as these systems can alleviate many drawbacks of conventional therapy. Metal-organic frameworks (MOFs), a new class of hybrid materials composed of metal ions and organic bridging ligands, have emerged as a promising platform for drug delivery, owing to their high drug loadings, biodegradability, and versatile functionality. The bulk MOF materials can absorb and release large amounts of therapeutics including ibuprofen, procainamide, and nitric oxide. Scale-down of MOFs to the nanoregime yields nanoscale metal-organic frameworks (NMOFs) that are more applicable as delivery vehicles, such as selective delivery of cisplatin prodrugs. Although progress has been made in utilizing NMOFs for drug delivery, many improvements must occur before they can become viable nanotherapeutics.

Figure 1

Formation of MOFs by coordination-directed self-assembly processes and the loading of drugs into MOFs via physical encapsulation. Only one unit of an infinite MOF framework is shown for clarity.

Figure 2

The structure of MIL-101. The tetrahedra are assembled from trivalent metal centers (Cr or Fe) and 1,4-benzenedicarboxylate. MIL-101 possesses larger cages than MIL-100, which facilitates Ibuprofen loading.

Figure 3

Absorption, storage, and release of nitric oxide (NO) in a Co or Ni MOF. Activation occurs by dehydration of the MOF at 110 °C, followed by NO loading at room temperature. Finally, delivery (release) of NO is triggered when the MOF was exposed to 11% relative humidity. (Pink spheres indicate water molecules, red and blue spheres indicate nitric oxide.)

Figure 4

A) Schematic showing the synthesis of Tb-DSCP NMOF (designated as NCP-1) and its subsequent coating with silica shell (NCP-1′) and conjugation with cyclic peptide. (PVP = polyvinylpyrollidone, TEOS = tetraethylorthosilicate) B) TEM micrograph for as-synthesized NCP-1. C) TEM and D) SEM micrographs for NCP-1′. E) In vitro cytotoxicity assay curves for HT-29 cells obtained by plotting the % cell viability against the Pt concentration of various samples and cisplatin control.

Figure 5

NanoMIL-101 can be loaded both with an optical imaging agent and cisplatin prodrug. Simultaneous release of the fluorophore and cisplatin prodrug allows real-time monitoring of the drug delivery by optical imaging.