Characterization of a Zeolite-Y-Encapsulated Zn(II)Salmphen Complex with Targeted Anticancer Property

Abstract

Resistance and severe side effects of classical chemotherapeutic drugs are major challenges to cancer therapy. New therapeutic agents and combination therapy are considered potential solutions that enhance the efficacy of the drug as well as reduce drug resistance. The success of a platinum-based anticancer drug, cisplatin, has paved the way to explore metal-centered anticancer therapeutic agents. Herein, the zeolite-Y-encapsulated Zn(II)Salmphen complex is synthesized using a flexible ligand approach. The Zn(II)Salmphen complex and its encapsulation within the supercage of zeolite-Y were characterized by elemental analysis, Fourier transform infrared (FTIR) spectroscopy, UV–vis, fluorescence, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), NMR, and high-resolution mass spectrometry (HRMS) techniques. Elemental analysis, PXRD, and SEM, all together confirm the integrity of the zeolite framework after the encapsulation of Zn(II)Salmphen complex in it, and elemental analysis provides the Si/Al ratio and Zn content present. FTIR and XPS studies indicate the successful encapsulation of the complex. NMR and HRMS studies confirm that the Zn(II)Salmphen complex is dimer; however, within the supercage of zeolite-Y, it is expected to exist as a monomer. The extent of structural modification of the encapsulated Zn(II)Salmphen complex is intimated by electronic spectroscopic studies. The free-state Zn(II)Salmphen is a fluorescent complex, and even the encapsulated Zn(II)Salmphen complex, when taken in dimethyl sulfoxide (DMSO), shows fluorescence. In comparison to cisplatin, encapsulated Zn(II)Salmphen complex displays comparable cytotoxicity (IC50 = 2.0 ± 0.5 μg/mL at 48 h) toward breast cancer cell line, whereas free Zn(II)Salmphen has better cytotoxicity (IC50 = 1.5 ± 0.5 μg/mL at 48 h). Importantly, elemental analysis has revealed that the IC50 value, if calculated only in terms of Zn(II)Salmphen within Zn(II)Salmphen-Y, is as low as 54.59 ng/mL, indicating a very high efficacy of the drug. Interestingly, a 48 h treatment with the encapsulated Zn(II)Salmphen complex shows no toxicity toward immortal noncancerous keratinocyte cells (HaCaT), whereas cisplatin has an IC50 value of 1.75 ± 0.5 μg/mL. Internalization studies indicate that zeolite-Y targets cancer cells better than it does noncancerous ones. Hence, cellular uptake of the zeolite-encapsulated Zn(II)Salmphen complex in cancer cells is more than that in HaCaT cells, resulting in the generation of more reactive oxygen species and cell death. Significant upregulation of DNA damage response protein indicates that DNA-damage-induced cellular apoptosis could be the mechanism of drug action. Overall, the zeolite-encapsulated Zn(II)Salmphen complex could be a better alternative to the traditional drug cisplatin with minimal effect on noncancerous HaCaT cells and can also be utilized as a fluorescent probe in exploring the mechanistic pathway of its activity against cancer cells.