Mentha mozaffarianii mediated biogenic zinc nanoparticles target selected cancer cell lines and microbial pathogens

Highlights

• The biosynthesis of zinc oxide nanoparticles (ZnO–NPs) using leaf extracts of Mentha mozaffarianii was accomplished.

• ZnO–NPs were strongly cytotoxic against selected cancerous cell lines, while being non–toxic to the normal cells.

• ZnO–NPs showed potent antimicrobial activity against gram–negative, gram–positive bacteria, and four fungi strains.

Abstract

Here we report the biosynthesis of zinc oxide nanoparticles (ZnO-NPs) using aqueous extract of medicinally active Mentha mozaffarianii for biomedical applications. ZnO-NPs were characterized by X-ray diffraction (XRD), Field Emission Scanning Electron Microscope (FE-SEM), Energy-dispersive X-ray (EDX) spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. The sharp and narrow diffraction peaks in the whole spectrum revealed that the ZnO-NPs are nanosized and well crystalized. FE-SEM analysis exhibited the spherical shape of the biosynthesized ZnO-NPs (mean diameter of about 20–29 nm). EDX analysis confirmed the formation of highly pure ZnO-NPs. ZnO-NPs exerted distinct effects on cancer cell lines while posing no impact on normal fibroblast cells. ZnO-NPs were primarily effective against HeLa (IC50: 50.1 μg/ml) cells, followed by MDA-MD231 (IC50: 54.9 μg/ml), and LS180 (63.4 μg/ml) cell lines. The biogenic ZnO-NPs revealed potent antimicrobial activity against two Gram-negative [Enterobacter aerogenes (maximum zone of inhibition (MZI): 20 mm) and Klebsiella pneumoniae (MZI: 22 mm)] and two Gram-positive [Bacillus subtilis (MZI: 23.2 mm) and Staphylococcus aureus] strains of bacteria, and four strains of fungi [C. glabrata (MZI: 17.5 mm), C. albicans (MZI: 21 mm), P. oryzae (MZI: 15 mm), C. neoformans (MZI: 16 mm)]. These findings provide preliminary information for the development of anticancer and antimicrobial drugs using biosynthesized ZnO-NPs.

Introduction

Nanoparticles (NPs) are used in practically every aspect of modern life. The unique size-dependent physicochemical and biological properties of NPs promote their potential utility in biological applications including nanomedicine [[1], [2], [3], [4], [5]]. Nanomedicine may be a proper approach in treating various diseases including different types of cancer [[6], [7], [8]], parasitic [e.g. 9] and microbial [e.g. 10] infections by means of offering lower dosage and side effect, better patient-to-patient consistency, bioavailability, target specificity and improved sensitivity of diagnosis [11]. Fundamentally, NPs can be classified into two broad groups including organic (i.e. carbonic nanostructures) and inorganic NPs. Inorganic NPs (e.g. metallic NPs) have attracted a great interest due to their availability, rich functionality, and good biocompatibility which have significant influences on many areas such as pharmaceutics [12]. Technically, metallic NPs have been synthesized using several different methods [13] such as chemical, physical and biological methods [14]. However, their synthesis by the conventional methods involves the utilization of toxic chemicals, which raises environmental and biological concerns [5,9,15,16]. To address such concerns, a great deal of effort has been put into the synthesis of metal NPs via biological (green) processes [17]. A number of biological resources like non-pathogenic [18] microorganisms including bacteria, actinomycetes, yeasts and fungi and even algae and plants have been reported for the biogenesis of NPs [[19], [20], [21]], but medicinally active plants have been in the limelight recently because of several distinct properties: The plant-mediated route is rapid, cost-effective and safe in comparison to other available options [22]. Additionally, this approach offers a simple method that is convenient for the large-scale production and provides an ecofriendly process minimizing the side effects of physical and chemical methods [2,13]. In the plant-mediated route, the biologically active phytochemicals play an especially important role due to their ability to act as reducing, capping and stabilizing agents of metallic ions [17]. Several metal nanoparticles such as copper (Cu), alginate magnesium (Mg), gold (Au), zinc (Zn), titanium (Ti), and silver (Ag) have been evaluated [23], among them Zn is among the most promising and interesting metallic elements employed in the biosynthesis of nanomaterials. It is a strong reducing agent and can be easily oxidized, to form zinc oxide (ZnO), which is very convenient for preparation of ZnO-NPs. The most notable features of ZnO nanomaterials are eco-friendly and biodegradability properties. Recent studies have shown that ZnO-NPs have potent toxicity to bacteria but exhibit minimal effects on human cells. ZnO has the proven biocompatibility profile and is not toxic to human cells and is generally recognized as safe by the United States Food and Drug Administration. On the other hand, there is also a controversial finding raised by the European consumer product that nano and microparticles of ZnO unlikely cause health issues when it is direct contact with the skin in the form of sunscreen [24].

Cancer is a leading cause of morbidities and mortalities among individuals, accounting for an estimated 9.6 million deaths, or one in six deaths, in 2018 [25], and almost 15% of mortality in women. Importantly, it was anticipated that the global market for cancer treatments will grow to reach US$150 billion by 2020 [26]. Cancer is much more frequent through low-income and middle-income countries, especially in Sub-Saharan Africa and South-East Asia compared to high-income countries, which may be attributed to the implementation and quality of screening programs as well as other socioeconomic and health parameters through high-income countries [8]. Several options such as surgery, chemotherapy, radiation therapy, immunotherapy, stem cell transformation, cancer vaccinations, photodynamic therapy, or a combination thereof are mainly used for cancer treatment, often accompanied by severe side effects [[27], [28], [29]]. Additionally, conventional therapies suffer from some limitations such as non-specificity, poor tumor bioavailability, and unfavorable pharmacokinetics [26].

On the other hand, large amounts of antibiotics used for human therapy resulted in the selection of pathogenic microorganisms resistant to multiple drugs. The outbreak of the infectious diseases caused by pathogenic microorganisms and escalating occurrence of dangerous resistant strains to clinically approved classes of drugs are well-recognized to be one of the most important current public health problems [30]. The ongoing need to develop novel and effective antimicrobial [10] and antitumor agents with minimal side effects on human cells has urged the research community to invest in various strategies, one of which is nanomedicine [11] using synthesized metallic NPs mediated by medicinally active plants.

Mentha mozaffarianii (Lamiaceae) is an aromatic plant endemic to southern Iran [31]. The species is well-known for its wide applications in the food, drug and cosmetics industries [32], and is traditionally used as an antiseptic and analgesic to treat painful menstruation, arthralgia, headache, fever, common cold, and wounds. It has also shown promise to effectively cure microbial infections [31,33].

This study highlights the anticancer activity of phyto-mediated biosynthesized ZnO-NPs using M. mozaffarianii extract against selected cancerous cell lines. In addition, the antibacterial and antifungal activities of the ZnO-NPs against some pathogenic bacteria and fungi strains was tested under laboratory conditions. The importance of the present work is viewed specially with respect to ascertaining the potential of a widely distributed under-utilized M. mozaffarianii as medicine. To the best of our knowledge, this is the first anticancer, antibacterial and antifungal study of M. mozaffarianii mediated biosynthesized ZnO-NPs.