Cyanobacteria are oxygenic prokaryotic phototrophs which are widespread in almost all types of habitats worldwide [1
]. Cyanobacteria present in the eastern region of the Kingdom of Saudi Arabia are diverse in their niches; some are marine, whilst others are freshwater types [2
]. The Arabian Gulf is reported to host several cyanobacterial genera, most commonly those belonging to filamentous forms.
Over the last three decades, a number of microorganisms and higher plants have been found to be competent, eco-friendly nano-factories for the synthesis of nanoparticles through mechanisms adapted by the organism to cleanse their environment from heavy metals and radionuclides [3
]. Amongst biological systems used, cyanobacteria and microalgae attract special attention since they not only have the ability to convert many toxic metals into non-hazardous physical and chemical forms including nanoparticles, but also have some other advantages over other organisms. Cyanobacteria and microalgae grow rapidly in rather inexpensive growth media and produce a large amount of biomass in a short time by converting CO2
into organic matter and releasing oxygen during photosynthesis, thereby cleaning up the environment and at the same time bioremediating toxic metals. Some cyanobacteria and algal genera such as Plectonema boryanum
and Sargassum wightii
have been reported for their ability to bioconvert effect of Au3+
and the subsequent formation of gold nanoparticles (GNPs) [4
]. Nanoparticles can be formed either by extracellular or intracellular enzymes [6
]. The reduction of gold ions may follow a similar pattern to silver ions, which possibly proceed through reductase enzymes and electron transporters as quinones, where the electrons produced are used to avoid metal ion damage in the presence of enzymes such as NADH-dependent reductases D [7
]. However, the intracellular formation of nanoparticles causes an imbalance in nutrient and substance exchange processes [8
]. The biological route for nanoparticles synthesis helps to avoid other chemical and physical routes with hazardous and toxic processing conditions and by products as well as allowing expensive synthesis of nanoparticles at physiological pH, temperature, and pressure. Moreover, nano-products synthesized through a biological route are expected to be biocompatible, therefore minimizing environmental and human health risks.
Metal nanoparticles are involved in many medical applications and possess a variety of pharmaceutical and pharmacological properties. One of the most outstanding applications for metal nanoparticles is their use in labeling and imaging, especially in magnetic resonance imaging, surface-enhanced Raman scattering, and fluorescence spectroscopy [9
]. Another popular use of metal nanoparticles is as optical or electrochemical biosensors [10
]. The use of metal nanoparticles in such techniques enabled their involvement in the medical and clinical diagnosis of many diseases such as cancer [12
], Alzheimer’s disease [13
], HIV [14
], hepatitis B [15
], tuberculosis [16
], diabetes [17
], and influenza [18
]. Metal nanoparticles have also been used as a treatment for many disorders and medical conditions such as cancer [19
] and rheumatoid arthritis [22
], and for several topical and systemic infections as anti-microbial agents [24
]. Metal nanoparticles are now recognized as an excellent drug delivery system due to their high biocompatibility and excellent conjugation ability with biological material such as DNA and RNA. Nanoparticles show good optical properties, enabling drug tracking and bioavailability studies [9
]. Working as drug vectors, metal nanoparticles can exhibit drug-targeting or gene-delivering properties [9
Myocardial infarction, a consequence of ischemic heart disease, is a leading cause of mortality worldwide. Many medicinal agents are now used to manage this condition depending on varied mechanisms of action including dissolving thrombosis and repair of infarcted area myocytes. The treatment of ischemic heart diseases, including infarction using metal nanoparticles, is a new approach and is little studied. Ahmed et al. [31
] have investigated the effect of metal nanoparticles on ischemia induced in the heart of experimental rats and the results indicated the curative activity of the nanoparticle on the infarcted heart.
To the best of the authors’ knowledge, there is no data available about the use of cyanobacteria from the eastern region of Saudi Arabia for the production of nanoparticles, despite their wide biodiversity. The main aim of this manuscript was to investigate the ability of the cyanobacterium Lyngbya majuscula to produce GNPs from externally supplied bulk ionic gold salt solution. The anti-myocardial infarction activity of the produced GNPs was investigated using a novel approach in which different treatments were prepared, including the cyanobacterial extract, GNP solution, and a combination of both.
The Arabian Gulf is a relatively small marine water body. Its salinity level is on the increase (nearly greater than 40 ppt) [46
]. This is due to its nature as a semi-closed water body as well as the fact that several huge desalination plants are operating in its coastal region. They desalinate water and dispose of the highly concentrated brine back into the Arabian Gulf, thereby increasing the salinity level greatly. The condition is exacerbated by the high water evaporation rate. This means that there is a great input of ions that is added to that water body. Another overlooked factor is ballast water that is being disposed of into the Arabian Gulf. Oil tankers from different parts of the world upload oil and dispose of ballast water containing contaminating residues into the Arabian Gulf. Only organisms with high ability to cope with such a contaminated and salinized habitat are able to survive. Other environmental challenges faced by those organisms are high solar irradiance and the nearly stagnant state of the water. Given all of these factors, it seems that cyanobacteria growing in such a niche have a rather unique metabolic activity that has enabled them to grow and detoxify harmful ions through reducing them into non-harmful nanoforms [47
With regard to the ability of the cyanobacterium L. majuscula
to reduce gold ions to metallic nanogold particles both intra- and extracellularly, Chakraborty et al. [49
] reported this phenomenon, which starts with metabolic-independent binding, followed by accumulation, and then reduction. Parial and Pal [50
] indicated the initial formation of gold nanoparticles intracellularly, followed by subsequent formation extracellularly. The reports assumed that abiotic factors, for example, presence of reducing moieties such as reducing sugars in the polysaccharide sheath and fatty acids in the plasma membrane, or other cellular reducing entities, might be involved in reducing gold ions. Biotic factors such as the involvement of reducing enzymes in reduction of gold cannot be excluded [47
As for extracellular-reducing activities, it is reported that parts of the polysaccharide sheath can dissociate from the filaments, forming what is known as exopolysaccharide into solution. This exopolysaccharide is known for its heavy metal-removing activity [51
] and its high content of reducing sugars that can be effective in reducing gold nanoparticles.
The surface plasmon resonance of gold nanoparticles is a result of interaction between oscillating electric fields of a light ray with the free electrons causing a concerted oscillation of electron charge that is in resonance with the frequency of visible light. As particle size increases, the wavelength of surface plasmon resonance-related absorption shifts to longer wavelengths. Red light is then absorbed, and blue light is reflected, yielding solutions with a pale blue or purple color.
The surface-active molecules on the cell surface of the cyanobacterium are suggested to be involved in the reduction of metal ions. However, their number may be not high enough to allow for the reduction of all ions at higher concentrations, i.e., the number of bioactive molecules and the number of cells present may be limiting factors for the number of ions to be reduced. Therefore, the synthesis of nanoparticles may be dependent on metal concentration as well as the number of the cells or the number of bioactive molecules present. This differential response indicates the possibility of custom designed nanoparticles by varying cell number and metal concentration in solution.
Environmental applications of nanogold related to color changes associated with their aggregation and/or local refractive index change have been exploited as optical sensing methods for the detection of toxins [52
], heavy metals, and other environmental pollutants [53
] in water, soil, and other environmental samples. GNPs are also utilized to enhance the performance of electrochemical sensors due to their catalytic properties [54
]. Electrochemical sensors have been widely investigated for environmental pollutants screens.
There are certain factors that can affect the efficiency and impact of nanoparticles, which include their size, shape, and distribution. Those factors are affected by synthesis procedures, reducing agents, and stabilizers. For example, small-sized nano-silver particles are more efficient as antimicrobial agents, probably due to ease of penetration of cellular membranes. The recently reviewed antibacterial modes of action of silver nanoparticles were found to be related to the induction of alterations of many cellular functions such as membrane permeability, respiratory activity, and DNA replication [55
]. With regard to GNPs, their antibacterial activity against acne or scurf is reported and they have commercial applications in soap and cosmetic industries. They can remove waste materials from skin and control sebum. GNP-mediated growth inhibition of different Gram-positive and Gram-negative bacteria and fungi has been recently reported [56
]. Functionalizing GNPs with polyethylene glycol increases stability, both in vivo and in vitro [57
]. The inert, non-toxic GNPs can be bio-synthesized in a range of sizes from 1 to 150 nm and can be readily functionalized with targeting ligands and drugs to allow delivery at the required site by way of their photophysical properties or by intercellular glutathione levels [57
]. Many hypotheses discussing the mechanism of nanoparticles formation by cyanobacteria [58
] suggested the involvement of the water-soluble pigment phycocyanin in the reduction of silver ions and/or other organic molecules, most likely polysaccharides. All were able to produce nanoparticles, reinforcing the hypotheses that both extracellular and intracellular moieties are able to reduce silver ions. Another hypothesis that cannot be excluded is the involvement of reducing enzymes such as NADH dependent reductases.
is a non-heterocystous filamentous cyanobacterium that is found in tropical and subtropical waterbodies. It is a well-known source of bioactive compounds producing an array of biologically active metabolites, which can be increased by factors such as stage of growth and light. The cyanobacterial extract is rich with a variety of these compounds, and a number of reviews have described some of these compounds and their activities [59
]. Examples of those compounds are thiazole peptides (pseudodysidenin, nordysidenin), barbamide (mixed polypeptide–polyketide), pseudodysidenin, nordysidenin, and apramides (linear peptides), and lyngbyapeptin A [61
The induction of myocardial infarction in a rat model using isoproterenol presents a non-invasive methodology for investigation of potential cardioprotective agents. Isoproterenol is a synthetic catecholamine, which induces myocardial infarction in rat models through several mechanisms such as increased water content, amplified oxidative stress, and infiltration of inflammatory cells to damaged areas [64
]. In the study herein, isoproterenol succeeded in the induction of myocardial infarction condition in rats as shown by elevated cardiac marker enzymes, irregularities in the heart rate, blood pressure and ECG parameters, and the depletion of the anti-oxidant enzymes (GRx and SOD). Treatment with cyanobacterial extract alone had no significant effect on the elevated cardiac marker enzymes, as can be seen from Figure 7
, Figure 8
and Figure 9
and Table 1
, however; it showed a noteworthy enhancement in antioxidant activity, as can be seen from Figure 10
. L. majuscula
possesses high diversity of active metabolites belonging to several classes of phytochemicals, and the cyanobacterium retains many pharmacological properties such as neurotoxic, cytotoxic, antimicrobial, and antiprotozoal activities [65
]. However, no metabolic miscellany and pharmacological actions were sufficient to induce the treatment of the myocardial infarction disorder. GNPs have been produced by L. majuscula
as a result of environmental incorporation of the gold ions by the cyanobacterium. The use of such GNP solutions alone or in combination with the cyano- bacterium has achieved effective management for cardiac infarction, as can be seen from the amendment of cardiac marker enzymes, reversal of ECG irregularities caused by isoproterenol, normalization of arterial pressure indices, and the elevation in antioxidant enzymes.
Although GNPs alone showed anti-myocardial infarction activity, addition of the cyanobacterial extract intensified this effect. Bearing in mind that the cyanobacterial extract did not show any activity on the ischemic heart, this synergetic activity could be explained through the presence of certain phytochemicals in the cyanobacterial extract that protect GNPs or alter their pharmacokinetics in the body including metabolism and excretion. For in vitro stabilization of GNPs, different agents are utilized, including thiols, surfactants, citrate, or phosphorus-containing ligands [66
]. As mentioned above, L. majuscule
comprises a high diversity of phytochemicals, including bioactive peptides [59
] (in particular thiazole peptides). Sulfur-containing compounds may act as a shield for GNPs surfaces through weak physical or strong chemical bonds [67
]. Therefore, it might be assumed that thiazole peptides in the bacterial extract may have some protective effect on the GNPs produced. Furthermore, the study strongly suggested the presence of a protein shell around the produced GNPs. Part of this protein shell could be attributed to the proteins and peptides found in the cyanobacteria itself. Continued supply of such proteins and peptides (in the form of cyanobacterial extract) could help the protection of the produced GNPs. In addition, the presence of such a shell around the GNPs can affect their metabolism in the body as well as their excretion rates, resulting in a prolonged and better effect. However, all the above is speculation based on some facts related to the cyanobacterium and GNPs, and further investigation is required.
The effect of gold nanoparticles on myocardial infarction was not intensively investigated previously [31
], and the effect of GNPs against doxorubicin-induced heart failure has been proven [68
]. However, the current study may add to the pool of knowledge on the activity of GNPs in myocardial infarction and tissue repair. To the best of the authors’ knowledge, this is the first study to discuss the myocardial infarction activity of GNPs produced by cyanobacteria and L. majuscula