Palladium nanoparticles encapsulated with resveratrol-derived phenols and polyphenols for targeted prostate cancer therapy

Includes vitaThe main goal of this dissertation was to explore the development of a new generation of green nanoformulations through the production of biocompatible palladium nanoparticles using resveratrol to treat, image and evaluate the efficacy of the formulations in prostate cancer cells with minimal toxicity to surrounding normal tissues. This dissertation is classified into three parts with three main objectives of the producing and characterizing resveratrol-derived phenols and polyphenols encapsulated palladium nanoparticles (Res-PdNPs) for the imaging and treatment of prostate cancer. Rigorous studies were performed for the optimization of the synthesis to achieve increased resveratrol-derived phenols and polyphenols corona loading on the palladium nanoparticle surface capable of providing adjuvant therapeutic benefits through delivering potent doses of both resveratrol phenols and nanoparticles directly to prostate cancer cells. A total of four formulations were produced Res-PdNP-1 (resveratrol-palladium nanoparticles), Res-PdNP-2 (increased resveratrol corona loaded palladium nanoparticles), Res-PdNP-3 (resveratrol-gum arabic stabilized palladium nanoparticles) and Res-PdNP-4 (increased resveratrol corona loaded and compacted with gum arabic stabilized palladium nanoparticles), respectively. Electron microscopic (TEM) results revealed that role of gum arabic was not limited to the stability of the nanoparticles but also facilitated the crystallization of the produced palladium nanoparticles (Res-PdNP-3 and Res-PdNP-4) and subsequently provided a supportive matrix for increased resveratrol phenols loading capacity. In vitro evaluation of the Res-PdNPs showed that Res-PdNP-1 and Res-PdNP-2, were not stable in serum while Res-PdNP-3 and Res-PdNP-4 maintained superior stability, thus ruling out further analysis using Res-PdNP-1 and Res-PdNP-2. The LC-MS/MRM results confirmed increased resveratrol phenols loading in Res-PdNP-4 when compared to Res-PdNP-3; consequently Res-PdNP-4 nanoparticles were confirmed as the ideal nanoformulation to improve the bioavailability, biodistribution and emblematize as an adjuvant therapy to induce selective and specific tumor-cell-death. The prostate tumor selective and specific affinity of Res-PdNP-4 nanoparticles through numerous cellular internalization studies undoubtedly revealed that Res-PdNP-4 nanoparticles can be internalized into prostate cancer cells via laminin receptor-mediated endocytosis which are receptors overexpressed on prostate cancer cells compared to normal cells. The Res-PdNP-4 nanoparticles were evaluated to investigate in vitro cellular toxicity against both prostate cancer (PC-3) cells and normal human aortic endothelial cells (HAEC). Results indicated that Res-PdNP-4 exhibited comparable anticancer efficacy against prostate cancer cells as chemotherapeutic drugs (cisplatin and etoposide). However, the results showed that cisplatin and etoposide treatments were highly toxic to normal cells while Res-PdNP-4 nanoparticles presented no toxicity further corroborating laminin receptor-mediated delivery, making Res-PdNP-4 nanoparticles selective and specific to prostate cancer cells. Res-PdNP-4 nanoparticles were investigated in vivo using a human prostate tumor-bearing severely combined immunodeficient (SCID) male mice as the animal model to evaluate Res-PdNP-4 nanoparticles ability to control or reduce prostate tumor size. The in vivo results of Res-PdNP-4 showed a good dose response which was well tolerated by the animals, as no animal health problems and discomfort was observed as evidenced by body weight/eating habits of animals. Although further studies are required to determine a better dose to see increased efficacy. This study was performed through intravenous (IV) administration of the Res-PdNP-4, intraperitoneal (IP) delivery and direct injection into the tumor may show a better response as has been the case with many different types of nanoparticles. In conclusion, the therapeutic efficacy results showed that Res-PdNP-4 have significant therapeutic effect and are able to control the tumor size in comparison to the saline control and free resveratrol treated groups. This was due to the high corona of resveratrol-derived phenols and polyphenols on the PdNPs facilitating effectively enhanced delivery of resveratrol with high bioavailability, giving an advantage in tumor therapy.Includes bibliographical reference

The enhancement of the activity of commercial antifungal agents using Aspalathus linearis synthesized gold nanoparticles

M.Sc.(Nanoscience)The synthesis and application of gold nanoparticles (AuNPs) has been intensively studied worldwide. However, the toxicity of these nanoparticles is still a concern. We considered that various physiochemical methods used to synthesize AuNPs are energy driven, costly and require the use of harmful chemicals. Thus, this makes them not environmentally-friendly. The aim of this study was therefore to synthesize AuNPs via a greener route using Aspalathus linearis tea leaves. The AuNPs were used to coat eight commercial antifungal discs (i.e. amphotericin B, fluconazole, clotrimazole, econazole, flucytosine, ketoconazole, miconazole and nystatin) against four Aspergillus spp. for enhanced antifungal activity. The aqueous extract of A. linearis was characterized by high performance liquid chromatography and liquid chromatography–mass spectroscopy. The AuNPs were characterized using ultravioletvisible (UV-vis) spectroscopy, dynamic light scattering, nanoparticle tracking analysis, Fourier transforms infrared spectroscopy (FTIR), high-resolution transmission electron microscopy and X-ray diffraction. The toxicity of the synthesized AuNPs was studied by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay and xCELLigence test on HepG-2 cell lines and results revealed very little to no toxicity of the AuNPs. The pristine antifungal and AuNPs coated antifungal discs were characterized by FTIR, scanning electron microscopy (SEM) and antifungal activity performed using the disc diffusion method. A strong resonance peak was observed at 529 nm of the AuNPs measured using UV-vis spectroscopy. Average size of AuNPs was ~44±1 nm and demonstrated excellent in-vitro stability under various solutions (5% NaCl, phosphate buffered saline) at varying pH levels. The SEM images revealed that the AuNPs were attached onto the coated antifungal discs when compared with the pristine antifungal discs. Antifungal results indicated that AuNPs significantly (p<0.001) enhanced the antifungal activity of the coated antifungal discs against the tested fungi when compared to the pristine antifungal discs. The AuNPs coated econazole disc exhibited the greatest (broad spectrum) activity than other antifungal agents tested. In conclusion, A. linearis can be used as a reducing agent in the synthesis of stable AuNPs. Furthermore, the AuNPs coated antifungal discs demonstrated considerable antifungal activity over the pristine antifungal discs..

The activity of gold nanoparticles synthesized using Helichrysum odoratissimum against Cutibacterium acnes biofilms

The human skin is home to millions of bacteria, fungi, and viruses which form part of a unique microbiome. Commensal microbes, including Cutibacterium acnes can occasionally become opportunistic resulting in the onset of dermatological diseases such as acne. Acne is defined as a chronic inflammatory disorder based on its ability to persist for long periods throughout an individual’s life. The synthesis of gold nanoparticles (AuNPs) was performed using the bottom-up approach by reduction of a gold salt (HAuCl4.3H2O) by the methanol extract (HO-MeOH) and aqueous decoction prepared from the dried aerial parts of Helichrysum odoratissimum (HOPowder). The HO-MeOH and HO-Powder AuNPs were prepared as unstabilised (GA) or stabilized (CGA) by the omission or addition of Gum Arabic (GA) as the capping agent. The characterization of the AuNPs was performed using Transmission Electron Microscopy (TEM), dynamic light scattering (DLS), Ultraviolet-Visual spectroscopy (UVVis), Thermogravimetric Analysis (TGA), X-Ray Diffraction (XRD) and Zeta-potential. The MBIC50 values for HO-MeOH GA and HO-MeOH C GA were 1.79 0.78% v/v and 0.22 0.16% v/v, respectively. The HO-Powder AuNPs showed potent inhibition of C. acnes cell adhesion to the 96-well plates. The HO-MeOH GA and HOPowder C GA exhibited IC50 of 22.01 6.13% v/v and 11.78 1.78% v/v, respectively. The activity of the AuNPs validated the anti-adhesion activity of the methanol extract in the crude form. The study emphasizes the selectivity of H. odoratissimum AuNPs for the prevention of C. acnes cell adhesion and not antimicrobial activity, which may prevent the emergence of resistant strains of C. acnes through reduced bactericidal or bacteriostatic activity, while targeting mechanisms of pathogenesis.The South African Research Chairs Initiative (SARChI) through the National Research Foundation (NRF).https://www.frontiersin.org/journals/cellular-and-infection-microbiology#am2022Plant Production and Soil Scienc