Fluorescent coumarin-modified mesoporous SBA-15 nanocomposite: Physico-chemical characterization and interaction with prokaryotic and eukaryotic cells

Highlights

• Three novel fluorescent composites were synthesized through immobilization of coumarins inside the channels of SBA-15.

• Their antioxidant, antimicrobial activity and cytotoxicity on HeLa-2 cells were evaluated.

• The obtained materials induce a depolarization effect on the bacterial cell membrane, which turns in a microbicidal effect.

Abstract

Three novel fluorescent mesoporous silica composites were obtained through the covalent immobilization of 7-amino-4-(trifluoromethyl)coumarin, 6-amino-chromen-2-one and 7-amino-4-methyl-3-coumarinylacetic acid, respectively, inside the channels of mesoporous silica SBA-15. Presence of fluorescent moieties was assessed by elemental analysis, thermal analysis, infrared, UV–Vis, ²⁹Si- and ¹³C-CP/MAS NMR, and fluorescence spectroscopy. Reduction of specific surface area of the composites by 50–60% and also the average pore size diameter by 0.5–0.55 nm compared to unfunctionalized SBA-15 was evidenced by N₂ adsorption desorption analysis. Their antioxidant, antimicrobial activity and cytotoxicity on HeLa-2 cells were evaluated in order to formulate some potential applications of the obtained compounds. The obtained results recommend the obtained fluorescent mesoporous nanocomposites as potential candidates for the development of novel probes for the in situ tracking of oxidative stress, as well as for antimicrobial applications.

Introduction

Since the discovery of mesoporous materials, researchers from all over the world have used them in numerous fields, from medicine to catalysis and others. Mesoporous silica particles have attracted much attention because of their chemical and thermal stabilities, high surface areas (ca. 1000 m²/g), high pore volumes (ca. 1 cm³/g), uniform and tunable pore sizes, nontoxic nature and a good biocompatibility [1,2]. Siliceous mesoporous materials have the advantage to be degradable in aqueous solutions, thus overcoming the problem of removing the material after use. In particular, SBA-15 (Santa Barbara Amorphous), represents one of the most important members of periodic mesoporous materials, due to its unique properties, including tunable pores, mechanical stability, large surface area and controllable thickness, making it interesting for science and technology applications [3]. One of the main applications of SBA-15 is that it can be used for the immobilization of drugs or other chemical compounds of interest. Various organic-inorganic hybrid composites were prepared by functionalization of SBA-15 with different molecules through the functional groups that can be grafted on its surface. The organic functionalization of mesoporous silica can tailor the surfaces properties, such as hydrophilicity or hydrophobicity and reactivity [3].

Coumarins, also known as benzopyran-2-ones, are an important class of natural heterocyclic compounds, low toxic on human organisms compared to other related compounds [[4], [5], [6]], that exhibit a wide variety of biological properties such us anticoagulant, antithrombotic, antitumor [7], anti-HIV [8,9], antimicrobial [10,11], antioxidant, anti-inflammatory [12,13] and antiviral [14] ones. Coumarins are found in high concentrations in fruit, seeds, leaves and roots [[15], [16], [17]]. Moreover, coumarins exhibit interesting fluorescence properties, that make them useful for developing composites with biomedical aplications. Fluorescence imaging of cells, tissues and organs is one of the most important technique in biomedical science and clinical diagnosis [18]. Some coumarin derivatives exhibit interesting fluorescence properties, making them useful for developing labeled composites with biomedical aplications. For example, 7-amino-4-methylcoumarin-3-acetic acid was used as a fluorecent imaging agent in the fluorohistochemical examination of human kidney glomeruli [19] and 3-(4-aminophenyl)-2H-chromen-2-one can be used for in situ fluorecent imaging of myelin in the vertebrates nervous system [20].

Some studies reported the use of coumarin derivatives combined with mesoporous silica nanoparticles (MSN) to obtain very efficient drug delivery systems. An excellent MSN based drug deliver system was reported for regulated anticancer drug chlorambucil release [21]. In this system, the 7-amino-coumarin grafted on MSN acted as both the “phototrigger” for the drug release and fluorescence group for cell luminescence imaging. Biological studies in vitro suggested that this drug carrier can effectively deliver the anticancer drug into intracellular environment and, hence, promote the drug action to kill the cancer cells upon irradiation. Wu et al. reported a photoresponsive nanosystem based on 7-hydroxy-4-bromomethyl coumarin covalently grafted on MSN to remotely control the sequential release of shRNA and DOX for optimizing and enhancing their synergistic therapy in multidrug-resistant HepG2/ADR human liver cancer cells [22]. Zhang et al. constructed a photoswitchable MSN with coumarin gates (MSNcg) as a general nanoplatform to collect cytosol peptides from live HeLa cells for the in situ and timed proteomic investigation [23]. MSNcg were the photocontrollable switches reversible under the control of UV irradiation with different wavelengths. In most of the reported studies, the main role of coumarine derivatives in the MSN-based delivery system was to trigger the release of the drug under suitable stimulus.

The main objective of our study was to obtain new fluorescent mesoporous silica composites through covalent immobilization of 7-amino-4-(trifluoromethyl)coumarin, 6-amino-chromen-2-one and 7-amino-4-methyl-3-coumarinylacetic acid, respectively, inside the channels of mesoporous silica SBA-15 and to investigate their antimicrobial and cytotoxic activity. As far as we know this is the first report regarding the potential use of the coumarin – mesoporous silica composites as antimicrobial and cytotoxic agents. Moreover, the inherent advantage of these materials is given by its fluorescence properties that allows easily monitoring. The paper describe the synthesis and physico-chemical characterization of the newly synthesized materials. Another important objective of this study was to investigate the in vitro interaction of the functionalized SBA-15 with prokaryotic and mammalian cells, in order to formulate some potential biological applications of these fluorecent mesoporous silica materials for research, diagnosis or treatment.