The Therapeutic Effect of Second Near-Infrared Absorbing Gold Nanorods on Metastatic Lymph Nodes via Lymphatic Delivery System.

Photothermal therapy has been established recently as a non-invasive treatment protocol for cancer metastatic lymph nodes. Although this treatment approach shows efficient tumour ablation towards lymph node metastasis, the monitoring and reporting of treatment progress using the lymphatic delivery channel still need to be explored. Herein, we investigated the anti-tumour effect of pegylated gold nanorods with a high aspect ratio (PAuNRs) delivered via the lymphatic route in a mouse model. In this study, breast carcinoma (FM3A-Luc) cells were inoculated in the subiliac lymph node (SiLN) to induce metastasis in the proper axillary lymph node (PALN). The treatment was initiated by injecting the PAuNRs into the accessory axillary lymph node (AALN) after tumour metastasis was confirmed in the PALN followed by external NIR laser irradiation under a temperature-controlled cooling system. The anti-tumour impact of the treatment was evaluated using an in vivo bioluminescence imaging system (IVIS). The results showed a time-dependent reduction in tumour activity with significant treatment response. Tumour growth was inhibited in all mice treated with PAuNRs under laser irradiation; results were statistically significant (** p < 0.01) even after treatment was concluded on day 3. We believe that this non-invasive technique would provide more information on the dynamics of tumour therapy using the lymphatically administered route in preclinical studies.

Cytotoxicity, fluorescence tagging and gene-expression study of CuInS/ZnS QDS - meso (hydroxyphenyl) porphyrin conjugate against human monocytic leukemia cells.

The toxicity of heavy metals present in binary semiconductor nanoparticles also known as quantum dots (QDs) has hindered their wide applications hence the advent of non-toxic ternary quantum dots. These new group of quantum dots have been shown to possess some therapeutic action against cancer cell lines but not significant enough to be referred to as an ideal therapeutic agent. In this report, we address this problem by conjugating red emitting CuInS/ZnS QDs to a 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin -photosensitizer for improved bioactivities. The glutathione capped CuInS/ZnS QDs were synthesized in an aqueous medium using a kitchen pressure cooker at different Cu: In ratios (1:4 and 1:8) and at varied temperatures (95 °C, 190 °C and 235 °C). Optical properties show that the as-synthesized CuInS/ZnS QDs become red-shifted compared to the core (CuInS) after passivation with emission in the red region while the cytotoxicity study revealed excellent cell viability against normal kidney fibroblasts (BHK21). The highly fluorescent, water-soluble QDs were conjugated to 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) via esterification reactions at room temperature. The resultant water-soluble conjugate was then used for the cytotoxicity, fluorescent imaging and gene expression study against human monocytic leukemia cells (THP-1). Our result showed that the conjugate possessed high cytotoxicity against THP-1 cells with enhanced localized cell uptake compared to the bare QDs. In addition, the gene expression study revealed that the conjugate induced inflammation compared to the QDs as NFKB gene was over-expressed upon cell inflammation while the singlet oxygen (1O2) study showed the conjugate possessed large amount of 1O2, three times than the bare porphyrin. Thus, the as-synthesized conjugate looks promising as a therapeutic agent for cancer therapy.

Application of Porphyrins in Antibacterial Photodynamic Therapy.

Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.

Encapsulation of Gold Nanorods with Porphyrins for the Potential Treatment of Cancer and Bacterial Diseases: A Critical Review.

Cancer and bacterial diseases have been the most incidental diseases to date. According to the World Health Report 2018, at least every family is affected by cancer around the world. In 2012, 14.1 million people were affected by cancer, and that figure is bound to increase to 21.6 million in 2030. Medicine therefore sorts out ways of treatment using conventional methods which have been proven to have many side effects. Researchers developed photothermal and photodynamic methods to treat both cancer and bacterial diseases. These methods pose fewer effects on the biological systems but still no perfect method has been synthesized. The review serves to explore porphyrin and gold nanorods to be used in the treatment of cancer and bacterial diseases: porphyrins as photosensitizers and gold nanorods as delivery agents. In addition, the review delves into ways of incorporating photothermal and photodynamic therapy aimed at producing a less toxic, more efficacious, and specific compound for the treatment.

Applications of functionalized nanomaterials in photodynamic therapy.

Specially designed functionalized nanomaterials such as superparamagnetic iron oxide, gold, quantum dots and up- and down-conversion lanthanide series nanoparticles have consistently and completely revolutionized the biomedical environment over the past few years due to their specially inferring properties, such as specific drug delivery, plasmonic effect, optical and imaging properties, therapeutic thermal energy productionand excellent irresistible cellular penetration. These properties have been used to improve many existing disease treatment modalities and have led to the development of better therapeutic approaches for the advancement of the treatment of critical human diseases, such as cancers and related malaise. In photodynamic therapy, for example, where the delivery of therapeutic agents should ideally avoid toxicity on nearby healthy cells, superparamagnetic iron oxide nanoparticles have been shown to be capable of making photodynamic therapy (PDT) prodrugs and their associative targeting moieties tumor-specific via their unique response to an external magnetic fields. In this review, the nanomaterials commonly employed for the enhancement of photodynamic therapy are discussed. The review further describes the various methods of synthesis and characterization of these nanomaterials and highlights challenges for improving the efficacy of PDT in the future.

An analysis of human exposure to trace elements from deliberate soil ingestion and associated health risks.

Fifty-seven samples of soils commonly ingested in South Africa, Swaziland, Democratic Republic of Congo (DRC), and Togo were analyzed for the concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni), and zinc (Zn) and their bioaccessibility in the human gastrointestinal tract. Bioaccessibility values were used to calculate daily intake, and hazard quotient of each trace element, and chronic hazard index (CHI) of each sample. Carcinogenic risk associated with As and Ni exposure were also calculated. Mean pseudo-total concentrations of trace elements in all samples were 7.2, 83.3, 77.1, 15.4, 28.6, 24.9, 56.1, 2.8, and 26.5 mg/kg for As, Cr, Mn, Co, Ni, Cu, Zn, Cd, and Pb, respectively. Percent bioaccessibility of Pb (13-49%) and Zn (38-56%) were highest among trace elements studied. Average daily intake values were lower than their respective reference doses for ell elements except for Pb in selected samples. Samples from DRC presented the highest health risks associated with trace element exposure with most of the samples having CHI values between 0.5 and 1.0. Some samples had higher than unacceptable values of carcinogenic risk associated with As and Ni exposure. Results indicate low trace element exposure risk from ingesting most of the soil samples.

A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy.

Systemic delivery of an anti-cancer agent often leads to only a small fraction of the administered dose accumulating in target sites. Delivering anti-cancer agents through the lymphatic network can achieve more efficient drug delivery for the treatment of lymph node metastasis. We show for the first time that polymeric gold nanorods (PAuNRs) can be delivered efficiently from an accessory axillary lymph node to a tumor-containing proper axillary lymph node, enabling effective treatment of lymph node metastasis. In a mouse model of metastasis, lymphatic spread of tumor was inhibited by lymphatic-delivered PAuNRs and near-infrared laser irradiation, with the skin temperature controlled by cooling. Unlike intravenous injection, lymphatic injection delivered PAuNRs at a high concentration within a short period. The results show that lymphatic administration has the potential to deliver anti-cancer agents to metastatic lymph nodes for inhibition of tumor growth and could be developed into a new therapeutic method.

Synthesis of Silver Nanoparticles Using Buchu Plant Extracts and Their Analgesic Properties.

We herein report for the first time the synthesis and analgesic properties of silver nanoparticles (Ag-NPs) using buchu plant extract. The as-synthesised Ag-NPs at different temperatures were characterised by UV-Vis spectroscopy, Fourier transform infra-red spectroscopy (FTIR) and transmission transform microscopy (TEM) to confirm the formation of silver nanoparticles. Phytochemical screening of the ethanolic extract revealed the presence of glycosides, proteins, tannins, alkaloids, flavonoids and saponins. The absorption spectra showed that the synthesis is temperature and time dependent. The TEM analysis showed that the as-synthesised Ag-NPs are polydispersed and spherical in shape with average particle diameter of 19.95 ± 7.76 nm while the FTIR results confirmed the reduction and capping of the as-synthesised Ag-NPs by the phytochemicals present in the ethanolic extract. The analgesic study indicated that the combined effect of the plant extract and Ag-NPs is more effective in pain management than both the aspirin drug and the extract alone.

Chemical composition and anti-inflammatory activities of the essential oils from Acacia mearnsii de Wild.

The volatile oils of the leaves and the stem bark of Acacia mearnsii de Wild obtained by hydro-distillation were analysed by gas chromatography-mass spectrometry. A total of 20, 38, 29 and 38 components accounted for 93.8%, 92.1%, 78.5% and 90.9% of the total oils of the fresh, dry leaves and fresh, dry stem bark, respectively. The major components of the oil were octadecyl alcohol (25.5%) and phytol (10.5%); cis-verbenol (29.5%); phytol (10.1%) and phytol (23.4%) for the fresh leaves, dried leaves, fresh stem, dry stem bark, respectively. Oral administration of essential oils at a dose of 2% showed significant (p < 0.05) anti-inflammatory properties in the albumin-induced test model in rats. Oils from the fresh leaves and dry stems inhibited inflammation beyond 4 h post treatment. The potent anti-inflammatory activity of essential oils of A. mearnsii hereby confirmed its traditional use in treating various inflammatory diseases.

Semi-synthesis of nitrogen derivatives of oleanolic acid and effect on breast carcinoma MCF-7 cells.

BACKGROUND: Oleanolic acid is a triterpenoid that has shown in vitro cytotoxic activity against human tumour cells and is known to be present in many higher plants. MATERIALS AND METHODS: Oleanolic acid is known to have some biological potential including anticancer property. Oleanolic acid was isolated from the ethyl acetate fraction of Syzygium aromaticum seed with an aim of dervitatising the functional group and evaluating the biological activities of the semi-synthesised compounds. Acylation of the alcohol functional group of the oleanolic acid afforded the opportunity of hydrazine reaction to give 3-acetoleanolic hydrazide. Further reaction of 3-acetoleanolic hydrazide with benzyladehyde, glacial acetic acid and methanol resulted in the synthesis of the corresponding 3-acetoxyoleanolic hydrazone. RESULTS: The semi-synthetic oleanolic acid derivatives did not exhibit enhanced cytotoxic activity over oleanolic acid itself. CONCLUSION: 3-acetoxyoleanolic hydrazide has a potent anticancer activity.

Completely green synthesis of dextrose reduced silver nanoparticles, its antimicrobial and sensing properties.

We herein report the green synthesis of highly monodispersed, water soluble, stable and smaller sized dextrose reduced gelatin capped-silver nanoparticles (Ag-NPs) via an eco-friendly, completely green method. The synthesis involves the use of silver nitrate, gelatin, dextrose and water as the silver precursor, stabilizing agent, reducing agent and solvent respectively. By varying the reaction time, the temporal evolution of the growth, optical, antimicrobial and sensing properties of the as-synthesised Ag-NPs were investigated. The nanoparticles were characterized using UV-vis absorption spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HR-TEM). The absorption maxima of the as-synthesized materials at different reaction time showed characteristic silver surface plasmon resonance (SPR) peak. The as-synthesised Ag-NPs show better antibacterial efficacy than the antibiotics; ciproflaxin and imipenem against Pseudomonas aeruginosa with minimum inhibition concentration (MIC) of 6 µg/mL, and better efficacy than imipenem against Escherichia coli with MIC of 10 µg/mL. The minimum bactericidal concentration (MBC) of the as-synthesised Ag-NPs is 12.5 µg/mL. The sensitivity of the dextrose reduced gelatin-capped Ag-NPs towards hydrogen peroxide indicated that the sensor has a very good sensitivity and a linear response over wide concentration range of 10(-1)-10(-6)M H2O2.

Green synthesis of silver nanoparticles using cellulose extracted from an aquatic weed; water hyacinth.

As part of the desire to save the environment through "green" chemistry practices, we herein report an environmentally benign synthesis of silver nanoparticles (Ag-NPs) using cellulose extracted from an environmentally problematic aquatic weed, water hyacinth (WH), as both reducing and capping agent in an aqueous medium. By varying the pH of the solution and reaction time, the temporal evolutions of the optical and morphological properties of the as-synthesised Ag-NPs were investigated. The as-synthesised cellulose capped silver nanoparticles (C-Ag-NPs) were characterised using Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRTEM). The maximum surface plasmon resonance (SPR) peak decreased as the pH increased indicating that an increase in the pH of the solution favoured the formation of smaller particles. In addition, instantaneous change in the colour of the solution from colourless to brown within 5 min at pH 11 showed that the rate of reduction is faster at this pH compared to those at lower pH. The TEM micrographs showed that the materials are small, highly monodispersed and spherical in shape. The average particle mean diameters were calculated to be 5.69±5.89 nm, 4.53±1.36 nm and 2.68±0.69 nm nm at pH 4, 8 and 11 respectively. The HRTEM confirmed the crystallinity of the material while the FTIR spectra confirmed the capping of the as-synthesised Ag-NPs by the cellulose. It has been shown therefore that based on this synthetic method, this aquatic plant can be used to the advantage of mankind.

A facile completely 'green' size tunable synthesis of maltose-reduced silver nanoparticles without the use of any accelerator.

A simple, straightforward, cost effective and environmentally benign method for the synthesis of highly stable and small sized silver nanoparticles (Ag-NPs) with narrow size distribution without the use of an accelerator is reported. Silver nitrate, gelatin and maltose, a non-toxic disaccharide sugar were used as silver precursor, stabiliser and reducing agent. By varying the precursor concentration and reaction time, we monitored the temporal evolution of the optical and structural properties of the as-synthesised Ag-NPs. The as-synthesised Ag-NPs were characterised using UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The absorption maxima of the surface plasmon resonance (SPR) were blue-shifted as the reaction time increased indicating decrease in particle size. The TEM images showed that, the particles are small, well dispersed and spherical in shape. The smallest particles with an average particle diameter of 3.76±1.00 nm and 4.09±1.83 nm were obtained at 24h for the 1.0M and 0.5M silver ion precursor solution concentration respectively. The smaller particles produced were attributed to the higher concentration of the reducing saccharides in the reaction system, which in turn increases the formation of stable silver ions in the reaction system. The HRTEM images confirmed the crystalline nature of the material while the FTIR confirmed the stabilisation of the Ag-NPs by the gelatin.