Adenosine/β-Cyclodextrin-Based Metal-Organic Frameworks as a Potential Material for Cancer Therapy

Abstract

Recently, researchers have employed metal-organic frameworks (MOFs) for loading pharmaceutically important substances. MOFs are a novel class of porous class of materials formed by the self-assembly of organic ligands and metal ions, creating a network structure. The current investigation effectively achieves the loading of adenosine (ADN) into a metal-organic framework based on cyclodextrin (CD) using a solvent diffusion method. The composite material, referred to as ADN:β-CD-K MOFs, is created by loading ADN into beta-cyclodextrin (β-CD) with the addition of K⁺ salts. This study delves into the detailed examination of the interaction between ADN and β-CD in the form of MOFs. The focus is primarily on investigating the hydrogen bonding interaction and energy parameters through the aid of semi-empirical quantum mechanical computations. The analysis of peaks that are associated with the ADN-loaded ICs (inclusion complexes) within the MOFs indicates that ADN becomes incorporated into a partially amorphous state. Observations from SEM images reveal well-defined crystalline structures within the MOFs. Interestingly, when ADN is absent from the MOFs, smaller and irregularly shaped crystals are formed. This could potentially be attributed to the MOF manufacturing process. Furthermore, this study explores the additional cross-linking of β-CD with K through the coupling of -OH on the β-CD-K MOFs. The findings corroborate the results obtained from FT-IR analysis, suggesting that β-CD plays a crucial role as a seed in the creation of β-CD-K MOFs. Furthermore, the cytotoxicity of the MOFs is assessed in vitro using MDA-MB-231 cells (human breast cancer cells).

Keywords: adenosine; cancer cells; inclusion complex; metal–organic framework; β-cyclodextrin.

Scheme 1

Schematic route of the ADN:β-CD-K MOFs.

Figure 1

Single-point energy for orientation 1 (A,D), orientation 2 (B,E) between guest, ADN, and the host, β-CD via PM3 calculation, and β-CD-K MOFs (C).

Figure 2

Interactions of hydrogen bonding for orientation 1 (A), and orientation 2 (B) with different atoms in the ADN:β-CD-K MOFs.

Figure 3

The energy values at HOMO and LUMO for ADN (A), β-CD-K MOFs (B), and ICs with orientations 1 (C), and 2 (D).

Figure 4

XRD patterns of β-CD-K MOFs, ADN:β-CD-K MOFs (A), and DSC of β-CD-K MOFs, and ADN:β-CD-K MOFs (B).

Figure 5

FE-SEM images of β-CD-K MOFs (A), ADN:β-CD-K MOFs (B), EDAX of β-CD-K MOFs (C), merged atoms (D), mapping of C (E), mapping of O (F), mapping of K with the β-CD-K MOFs (G), EDX of ADN:β-CD-K MOFs (H), merged atoms (I), mapping of C (J), mapping of O (K), mapping of K (L), and mapping of N with the ADN:β-CD-K MOFs (M).

Figure 6

AFM pictures of β-CD-K MOFs (A–C), and ADN:β-CD-K MOFs (D–F).

Figure 7

Survey scan spectra of β-CD-K MOFs (A), elemental spectra of C 1s (B), O 1s (C), K 2p (D), Survey scan spectra of ADN:β-CD-K MOFs (E), elemental spectra of C 1s (F), O 1s (G), K 2p (H), and N 1s (I).

Figure 8

FT-IR spectra of ADN, β-CD-K MOFs, and ADN:β-CD-K MOFs (A), and Raman spectra of ADN, β-CD-K MOFs, and ADN:β-CD-K MOFs (B).

Figure 9

¹H NMR spectra of ADN (A), ADN:β-CD-K MOFs (B), numbering of ADN for NMR interpretation (C), and the proposed structure of ADN:β-CD-K MOFs based on NMR interpretation (D).

Figure 10

In vitro drug release profile of ADN from ADN:β-CD-K MOFs under different pH conditions.

Figure 11

The in vitro cytotoxicity of MOFs on (A) MRC-5 cells and (B) MDA-MB-231 cells.

Figure 12

Fluorescence microscopic (bright field specification: magnification with 10× and scale bar 100 µm) image of MRC-5 cell lines with control (A), ADN (B), ADN:β-CD-K MOFs (C), fluorescence microscopic image of MDA-MB-231 cell lines with control (D), ADN (E), and ADN:β-CD-K MOFs (F).