Targeted Delivery of Lidocaine in Breast Cancer Cells via Zeolitic Imidazolate Framework-8 Nanoparticles

Abstract

The aim of this article is to use zeolitic imidazolate framework-8 (ZIF-8) metal-organic frameworks (MOFs) as drug delivery system for lidocaine, a local anesthetic with recently discovered antitumoral effects, in particular for the early-stage treatment of breast cancer. A previously optimized ZIF-8 synthetic method is employed, and the prepared material is deeply characterized with X-ray powder diffraction (XRPD), surface area analysis, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). After confirming the successful synthetic outcomes, a tailored loading procedure is developed to incorporate lidocaine within the ZIF-8 pores. The effectiveness of this loading process is verified using UV-Vis spectroscopy and TGA, while SEM and attenuated total reflectance-mid infrared spectroscopy further confirms the presence of lidocaine within the MOF pores. Afterwards, the pH-responsive drug release by dialyzing the lidocaine@ZIF-8 sample is tested either at physiological or at weakly acid pH values by UV spectroscopy on the dialysis solutions. Finally, the MDA-MB-231 breast cancer cells viability of lidocaine@ZIF-8 system is tested and compared with the free drug and the MOF alone, confirming its significant capabilities in the reduction of cells viability.

Keywords: ZIF‐8 nanoparticles; anticancer application; lidocaine; pH‐regulated delivery; targeted delivery.

Figure 1

Schematic representation of the hydrothermal synthesis of ZIF‐8. The MOF structure has been obtained using iRASPA software.^{[ 40 ]} Atoms color code: Zn (red), C (gray), and N (violet).

Figure 2

SEM images collected at a) 50 kX and b) 10 kX of as‐prepared ZIF‐8.

Figure 3

XRPD patterns of ZIF‐8 (orange) and lidocaine@ZIF‐8 (blue).

Figure 4

ATR‐MIR spectra of pure lidocaine (green), ZIF‐8 (orange), and lidocaine@ZIF‐8 (blue).

Figure 5

Drug release as a function of time obtained from UV–Vis data of the dialysis solution at pH = 5.5 and pH = 7.4, respectively.

Figure 6

Effect of lidocaine@ZIF‐8 on MDA‐MB‐231 breast cancer cells viability: MDA‐MB‐231 have been plated at a density of 9000 cells cm⁻² and, the day after, treated for a) 24, b) 48, and c) 72 h, with vehicle, lidocaine 0.01 mg mL⁻¹, ZIF‐8 0.01 mg mL⁻¹, and lidocaine@ZIF‐8 0.01 mg mL⁻¹, respectively. Cells viability was assessed by MTT assay (Number of independent experiment (N) = 3; *p‐value (p)<0.05, **p < 0.01 versus Lidocaine@ZIF‐8 0.01 mg mL⁻¹; paired t‐test; dot line  =  vehicle set at 1).