Inhibition of Breast Cancer Cell Proliferation by 9-Hydroxycamptothecin-Loaded Zeolitic Imidazolate Nanoparticles.

Abstract

Objectives: Novel drug delivery systems have been designed to enhance local drug concentrations while reducing side effects conducive to improved breast cancer treatment outcomes. This study aimed to identify the anti-cancer function of zeolite imidazole ester-based material loaded with camptothecin nanoparticles.

Methods: We utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin nanoparticles and investigated their impact on breast cancer cell proliferation. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin, characterized by a reduction in surface smoothness, accompanied by slight collapses and folds on the particle surface. Notably, we detected vibration of the benzene ring in the 9-hydroxycamptothecin structure within the nanoparticles. Cell proliferation was tested by CCK-8. Protein expression was measured by Western blot. The efficacy of nanoparticles was evaluated by animal experiments.

Results: In this study, we utilized a zeolitic imidazolate backbone material to fabricate 9-hydroxycamptothecin (9-HCPT) nanoparticles and investigated their impact on breast cancer cell proliferation. Scanning electron microscopy and Fourier-transform infrared spectroscopy revealed changes in the carrier skeleton of the loaded 9-hydroxyl camptothecin, characterized by a reduction in surface smoothness, accompanied by slight collapses and folds on the particle surface. Notably, we detected vibration of the benzene ring in the 9-HCPT structure within the nanoparticles. Using the CCK-8 method, we evaluated the inhibitory effect of these nanoparticles on breast cancer cells and observed a significant reduction in the cytotoxicity of camptothecin (CPT) when incorporated into the zeolite imidazole ester skeleton material. Immunoblot analysis showed upregulation of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and NF-κB-p65 in response to the nanoparticles. These results showed that our nanoparticles might be a useful drug delivery strategy to overcome breast cancer drug resistance.

Conclusion: The findings of this study suggest that nanoparticles loaded with CPT and formed from zeolite imidazole ester backbone material possess immune-enhancing properties that could suppress breast cancer progression. Accordingly, these nanoparticles hold promise as potential lead compounds for combined immunotherapy in breast cancer treatment.