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"gold nanoparticles"
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Diagnosis of tuberculosis by nanoparticle-based immuno-PCR assay based on mycobacterial MPT64 and CFP-10 detection
To improve the diagnostic accuracy of immuno-PCR (I-PCR) in tuberculosis (TB) patients by using functionalized gold nanoparticles (AuNPs) coupled with detection antibodies and oligonucleotides, and magnetic beads (MBs) conjugated with capture antibodies in the liquid phase.
MB-coupled AuNP-based I-PCR (MB-AuNP-I-PCR) assay was designed to detect a cocktail of
MPT64 and CFP-10 proteins in bodily fluids of TB patients.
The sensitivities of 89.3 (n = 94) and 78.1% (n = 73) were observed in pulmonary TB and extrapulmonary TB patients, respectively, with specificities of 97.9–98.3%. Notably, the sensitivities attained by MB-AuNP-I-PCR in smear-negative pulmonary TB and extrapulmonary TB patients were significantly higher (p < 0.05–0.001) than Magneto-ELISA and GeneXpert assay.
The improved technology, as well as enhanced diagnostic accuracy of MB-AuNP-I-PCR, may lead to development of an attractive diagnostic kit.
Journal Article
Novel route synthesis of porous and solid gold nanoparticles for investigating their comparative performance as contrast agent in computed tomography scan and effect on liver and kidney function
Gold nanoparticles (GNPs) with dimension in the range of 1-100 nm have a prominent role in a number of biomedical applications like imaging, drug delivery, and cancer therapy owing to their unique optical features and biocompatibility. In this work, we report a novel technique for the synthesis of two types of GNPs namely porous gold nanoparticles (PGNPs) and solid gold nanoparticles (SGNPs). PGNPs of size 35 nm were fabricated by reduction of gold (III) solution with lecithin followed by addition of L-ascorbic acid and tri-sodium citrate, whereas SGNPs with a dimension of 28 nm were prepared by reflux method using lecithin as a single reducing agent. Comparative studies using PGNPs (λ
560 nm) and SGNPs (λ
548 nm) were conducted for evaluating their use as a contrast agent. These studies reveled that in direct computed tomography scan, PGNPs exhibited brighter contrast (45 HU) than SGNPs (26 HU). To investigate the effect of PGNPs and SGNPs on the liver and kidney profile, male rabbits were intravenously injected with an equal dose of 1 mg/kg weight of PGNPs and SGNPs. The effect on biochemical parameters was evaluated 72 hours after intravenous (IV) injection including liver function profile, renal (kidney) function biomarker, random blood glucose value, and cholesterol level. During one comparison of contrast in CT scan, PGNPs showed significantly enhanced contrast in whole-rabbit and organ CT scan as compared to SGNPs 6 hours after injection. Our findings suggested that the novel PGNPs enhance CT scan image with higher efficacy as compared to SGNPs. The results showed that IV administration of synthesized PGNPs increases the levels of aspartate aminotransferase (AST), alkaline phosphate (ALP), serum creatinine, and blood glucose, whereas that of SGNPs increases the levels of AST, ALP, and blood glucose.
Journal Article
Parallel multi-parameter study of PEI-functionalized gold nanoparticle synthesis for bio-medical applications: part 1—a critical assessment of methodology, properties, and stability
Cationic polyethyleneimine (PEI)-conjugated gold nanoparticles (AuNPs) that are chemically and physically stable under physiological conditions are an ideal candidate for certain bio-medical applications, in particular DNA transfection. However, the issue remains in reproducibly generating uniform stable species, which can cause the inadequate characterization of the resulting product under relevant conditions and timepoints. The principal objective of the present study was to develop an optimized and reproducible synthetic route for preparing stable PEI-conjugated AuNPs (Au-PEIs). To achieve this objective, a parallel multi-parametric approach involving a total of 96 reaction studies evaluated the importance of 6 key factors: PEI molar mass, PEI structure, molar ratio of PEI/Au, concentration of reaction mixtures, reaction temperature, and reaction time. Application of optimized conditions exhibited narrow size distributions with characteristic surface plasmon resonance absorption and positive surface charge. The optimized Au-PEI product generated by this study exhibits exceptional stability under a physiological isotonic medium (phosphate-buffered saline) over 48 h and shelf-life in ambient condition without any significant change or sedimentation for at least 6 months. Furthermore, the optimized Au-PEI product was highly reproducible. Contributions from individual factors were elucidated using a broad and orthogonal characterization suite examining size and size distribution, optical absorbance, morphological transformation (agglomeration/aggregation), surface functionalities, and stability. Overall, this comprehensive multi-parametric investigation, supported by thorough characterization and rigorous testing, provides a robust foundation for the nanomedicine research community to better synthesize nanomaterials for biomedical use.
Journal Article
Ultra-stable and highly reactive colloidal gold nanoparticle catalysts protected using multi-dentate metal oxide nanoclusters
Owing to their remarkable properties, gold nanoparticles are applied in diverse fields, including catalysis, electronics, energy conversion and sensors. However, for catalytic applications of colloidal gold nanoparticles, the trade-off between their reactivity and stability is a significant concern. Here we report a universal approach for preparing stable and reactive colloidal small (~3 nm) gold nanoparticles by using multi-dentate polyoxometalates as protecting agents in non-polar solvents. These nanoparticles exhibit exceptional stability even under conditions of high concentration, long-term storage, heating and addition of bases. Moreover, they display excellent catalytic performance in various oxidation reactions of organic substrates using molecular oxygen as the sole oxidant. Our findings highlight the ability of inorganic multi-dentate ligands with structural stability and robust steric and electronic effects to confer stability and reactivity upon gold nanoparticles. This approach can be extended to prepare metal nanoparticles other than gold, enabling the design of novel nanomaterials with promising applications.
For catalytic nanoparticles there is often a trade-off between stability and activity. Here the authors report a route to ultra-stable and catalytically active colloidal small (~3 nm) gold nanoparticles using multi-dentate polyoxometalates as protecting agents in nonpolar solvents.
Journal Article
Smart gold nanoparticles enhance killing effect on cancer cells
The present study explored the cellular uptake dynamics, the subcellular location and the internalization mechanisms of gold nanoparticles (GNPs) and glucose-capped GNPs (Glu-GNPs). The cancer radiotherapy-enhancing effects of GNPs were also evaluated. We synthesized the GNPs and Glu-GNPs by the seeding technique. The effects on cellular uptake and the radiosensitizing effect induced by GNPs and Glu-GNPs at lower doses were investigated using two human cancer cell lines (HeLa and MCF-7). The intracellular location of the nanoparticles was analyzed by transmission electron microscopy (TEM). Analysis of cellular apoptosis following GNP-based radiotherapy was performed by flow cytometry and TUNEL assay. Cancer cells took up more Glu-GNPs than naked GNPs and the uptake curve showed size- and cell-dependent uptake. GNPs were mainly located in the cytoplasm and endocytosis is the mechanism behind the internalization of GNPs and Glu-GNPs. Lower doses of GNPs and Glu-GNPs still enhanced the killing effect using X-ray irradiation, although the apoptotic rate was not altered. The results presented in this study provide evidence that Glu-GNPs may have a bright future in tumor-targeted diagnosis and treatment.
Journal Article
A review of small molecules and drug delivery applications using gold and iron nanoparticles
Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their \"superparamagnetic\" properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents.
Journal Article
Biological Synthesis of Bioactive Gold Nanoparticles from Inonotus obliquus for Dual Chemo-Photothermal Effects against Human Brain Cancer Cells
The possibility for an ecologically friendly and simple production of gold nanoparticles (AuNPs) with Chaga mushroom (Inonotus obliquus) (Ch-AuNPs) is presented in this study. Chaga extract’s reducing potential was evaluated at varied concentrations and temperatures. The nanoparticles synthesized were all under 20 nm in size, as measured by TEM, which is a commendable result for a spontaneous synthesis method utilizing a biological source. The Ch-AuNPs showed anti-cancer chemotherapeutic effects on human brain cancer cells which is attributed to the biofunctionalization of the AuNPs with Chaga bioactive components during the synthesis process. Further, the photothermal ablation capability of the as-prepared gold nanoparticles on human brain cancer cells was investigated. It was found that the NIR-laser induced thermal ablation of cancer cells was effective in eliminating over 80% of the cells. This research projects the Ch-AuNPs as promising, dual modal (chemo-photothermal) therapeutic candidates for anti-cancer applications.
Journal Article
Mechanistic insights into melanin-induced PCR inhibition and its NanoPCR-based mitigation
Melanin is a potent inhibitor of PCR, which interferes with forensic DNA typing by binding to Taq polymerase and disrupting its function, leading to allele dropout and decreased peak heights. Traditional mitigation measures, such as dilution and replacement of the polymerase, often result in the loss of DNA and are not suitable for low-template forensic samples. In this study, melanin-induced inhibition was explored using molecular docking and dynamics simulation, which identified stable interaction with catalytic residues TYR671 and PHE667 (Kd = 31.76 ± 0.02 µM), thereby interfering with polymerase function. STR typing of the inhibitor-treated sample showed a total allelic loss of SE33 and Penta E, dropout at D12S391, and substantially reduced peak heights. The overall peak height was 443,409.3 RFU. Facilitating methods using AuNPs, BSA-coated AuNPs, and standard BSA were further compared. AuNPs provided partial restoration (TPH = 545,605.7 RFU), whereas BSA-coated AuNPs provided improved restoration (TPH = 682,938.3 RFU) with harmonious heterozygous peaks (mean PHR = 0.90). Standard BSA had the highest restoration (TPH = 786,122.7 RFU; mean PHR = 0.92), restored alleles between dye channels. Statistical analysis revealed significant enhancement by BSA (
p
< 0.0001) and moderate enhancement by BSA-coated AuNPs (
p
= 0.0186). The BSA yielded optimal results, but it also exhibited larger sample differences. On the other hand, BSA-coated AuNPs offered more consistent facilitation at a very low concentration compared to BSA. This study thus explains the mode of PCR inhibition by melanin. It further demonstrates that BSA remains the most effective facilitator, but it also has its own limitations. In contrast, BSA-coated AuNPs offer a reliable nanotechnology-based method to overcome this limitation in forensic PCR applications.
Journal Article
Optimally biosynthesized, PEGylated gold nanoparticles functionalized with quercetin and camptothecin enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities
Background
The development of nano delivery systems is rapidly emerging area of nanotechnology applications where nanomaterials (NMs) are employed to deliver therapeutic agents to specific site in a controlled manner. To accomplish this, green synthesis of NMs is widely explored as an eco-friendly method for the development of smart drug delivery system. In the recent times, use of green synthesized NMs, especially metallic NMs have fascinated the scientific community as they are excellent carriers for drugs. This work demonstrates optimized green, biogenic synthesis of gold nanoparticles (AuNPs) for functionalization with quercetin (QT) and camptothecin (CPT) to enhance potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs.
Results
Gold nanoparticles were optimally synthesized in 8 min of reaction at 90 °C, pH 6, using 4 mM of HAuCl
4
and 4:1 ratio of extract
:
HAuCl
4
. Among different capping agents tested, capping of AuNPs with polyethylene glycol 9000 (PG9) was found best suited prior to functionalization. PG9 capped AuNPs were optimally functionalized with QT in 1 h reaction at 70 °C, pH 7, using 1200 ppm of QT and 1:4 ratio of AuNPs-PG9:QT whereas, CPT was best functionalized at RT in 1 h, pH 12, AuNPs-PG9:CPT ratio of 1:1, and 0.5 mM of CPT. QT functionalized AuNPs showed good anti-cancer activity (IC
50
687.44 µg/mL) against MCF-7 cell line whereas test of anti-inflammatory activity also showed excellent activity (IC
50
287.177 mg/L). The CAM based assessment of anti-angiogenic activity of CPT functionalized AuNPs demonstrated the inhibition of blood vessel branching confirming the anti-angiogenic effect.
Conclusions
Thus, present study demonstrates that optimally synthesized biogenic AuNPs are best suited for the functionalization with drugs such as QT and CPT. The functionalization of these drugs with biogenic AuNPs enhances the potential anti-inflammatory, anti-cancer and anti-angiogenic activities of these drugs, therefore can be used in biomedical application.
Journal Article