Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

Abstract

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH₂-DTPA-Gd³⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd³⁺. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC₅₀ concentration of 12.6 mg/mL compared to an EC₅₀ concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH₂-DTPA-Gd³⁺-MIH and its potential to enhance breast cancer management.

Keywords: MCM-41; MIH 2.4Bl; MRI; breast cancer; contrast agent; gadolinium; mesoporous silica nanoparticle; theranostics.

Figure 1

(A) Representative images of the synthesized MCM-41 nanomaterial were obtained by scanning electron microscopy (SEM) at a magnification of 160,000× and (B) transmission electron microscopy (TEM) at a magnification of 120,000×.

Figure 2

(A) FTIR analysis comparing unmodified MCM-41 (blue line) and CTAB-modified MCM-41-CTAB (black line) (B) N₂ adsorption (■) and desorption (●) isotherms of the MCM-41 nanomaterial.

Figure 3

(A) FTIR spectra of unmodified MCM-41 (blue line) and amine-functionalized MCM-41-NH₂ (red line). Illustration of C-H bonds is shown in the orange circle. (B) Absorbance spectra from a colorimetric assay using the ninhydrin reagent, demonstrating the presence of primary amino groups on MCM-41-NH₂ (red line) compared to unmodified MCM-41 (blue line).

Figure 4

(A) FTIR spectra displaying changes post-conjugation of MCM-41-NH₂ with DTPA (purple line) and its complexation with Gd³⁺ (green line) (B) Gadolinium ion concentrations in the MCM-41-NH₂-DTPA-Gd³⁺ nanomaterial (●) measured by ICP-OES analysis after four sequential washes.

Figure 5

(A) Adsorption kinetics (●) and (B) release profile (●) of the mesoionic drug MIH 2.4Bl from the MCM-41-NH₂-DTPA-Gd³⁺ nanomaterial as a function of time. Each data point represents the mean ± standard deviation of three replicates.

Figure 6

MTT assay results showing the cell viability of (A) MDA-MB-231 breast cancer cells and (B) normal human mammary epithelial cells (HMECs) after 96 h of treatment with increasing concentrations of MCM-41-NH₂-DTPA-Gd³⁺ (●) and MCM-41-NH₂-DTPA-Gd³⁺-MIH (●) nanoparticles. The dashed lines represent 50% normalized cell viability. Each data point represents the mean ± standard deviation of three replicates.

Figure 7

(A) T₁-weighted magnetic resonance imaging (MRI) image of the MCM-41-NH₂-DTPA-Gd³⁺-MIH nanomaterial at various Gd³⁺ concentrations in DIUF water and (B) linear fitting of the normalized voxel values of 2D ROIs as a function of Gd³⁺ concentration in DIUF water (●). Each data point represents the mean ± standard deviations from two duplicate phantoms. (C) Relaxation rate of MCM-41-NH₂-DTPA-Gd³⁺-MIH (1/T₁) at 1.3 T (●). Each data point represents the mean ± standard deviation of three replicates.

Figure 8

Representative MRI scans of BALB/c mice with 4T1 tumors (A) before and (B) at 15 min after intratumoral injection with MCM-41-NH₂-DTPA-Gd³⁺-MIH nanomaterial. The scans show the T₁-weighted MRI signal intensity in various tissues. The tumor regions are highlighted by the red circles.