Facile Synthesis and Characterization of Uniform Au Nanospheres Capped by Citrate for Biomedical Applications.

We report a simple and versatile method for effectively replacing the toxic ligands, such as cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC), on the surface of Au nanospheres with different sizes by citrate. The method involves the deposition of an ultrathin shell of fresh Au in the presence of sodium citrate at an adequate concentration. After the ligand exchange process, multiple techniques are used to confirm that the surface of the resultant Au nanospheres is covered by citrate while there is no sign of aggregation. We also demonstrate the mitigation of cell toxicity after exchanging the surface-bound CTAB/CTAC with citrate, opening the door to a range of biomedical applications.

Gold-nanosphere mitigates osteoporosis through regulating TMAO metabolism in a gut microbiota-dependent manner.

Osteoporosis (OP) is a metabolic bone disease characterized by decreased bone mass and increased bone fragility. The imbalance of bone homeostasis modulated by osteoclasts and osteoblasts is the most crucial pathological change in osteoporosis. As a novel treatment strategy, nanomedicine has been applied in drug delivery and targeted therapy due to its high efficiency, precision, and fewer side effects. Gold nanospheres (GNS), as a common kind of gold nanoparticles (GNPs), possess significant antimicrobial and anti-inflammatory activity, which have been applied for the treatment of eye diseases and rheumatoid arthritis. However, the effect of GNS on osteoporosis remains elusive. In this study, we found that GNS significantly prevented ovariectomy (OVX)-induced osteoporosis in a gut microbiota-dependent manner. 16S rDNA gene sequencing demonstrated GNS markedly altered the gut microbial diversity and flora composition. In addition, GNS reduced the abundance of TMAO-related metabolites in OVX mice. Low TMAO levels might alleviate the bone loss phenomenon by reducing the inflammation response. Therefore, we investigated the alteration of cytokine profiles in OVX mice. GNS inhibited the release of pro-osteoclastogenic or proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin (IL)-6, and granulocyte colony-stimulating factor (G-CSF) in the serum. In conclusion, GNS suppressed estrogen deficiency-induced bone loss by regulating the destroyed homeostasis of gut microbiota so as to reduce its relevant TMAO metabolism and restrain the release of proinflammatory cytokines. These results demonstrated the protective effects of GNS on osteoporosis as a gut microbiota modulator and offered novel insights into the regulation of the "gut-bone" axis.

Triple-color fluorescence co-localization of PD-L1-overexpressing cancer exosomes.

Programed cell death ligand 1 (PD-L1) is a protein biomarker overexpressed on exosomes derived from tumor cells. It plays an important role in tumor diagnosis, screening, evaluation of therapeutic efficacy, and prognosis. In this study, a facile method is presented to detect PD-L1-overexpressing cancer exosomes with high specificity and sensitivity. First, gold nanospheres (GNSs) were attached to the bottom of an eight-well chambered slide by electrostatic adsorption, forming the detection substrate. Then, Cy5-labeled CD63 aptamers (i.e., the capture probes) were modified on the GNSs by Au-S bond. After adding samples containing target exosomes which were stained by membrane dyes DiI in advance, FAM-labeled PD-L1 aptamers (i.e., the immunoprobes) were added to recognize PD-L1 on the target exosomes. By triple-color fluorescence co-localization (TFC) of the Cy5, DiI, and FAM channels, highly sensitive and reliable detection of the PD-L1-overexpressing exosomes was achieved in the concentration range 7.78 × 101 to 7.78 × 104 particles/mL with a detection limit down to 6 particles/mL. The advantages of the proposed detection method include the following; first, the detection substrate is easy to prepare and convenient to clean. Second, the TFC strategy can completely exclude nonspecific reaction sites and thus significantly improves the accuracy. Such a facile and reliable detection method holds a great potential in exosome-based cancer theranostics. In this paper, we proposed a triple-color fluorescence co-localization (TFC) strategy to significantly improve the reliability of exosome detection and the detection substrate is easy to prepare and convenient to clean. In addition, the LOD is down to 6 particles/mL, which is quite low compared with other detection methods.

Quantifiable Effect of Interparticle Plasmonic Coupling on Sensitivity and Tuning Range for Wavelength-Mode LSPR Fiber Sensor Fabricated by Simple Immobilization Method.

Herein a gold nanosphere (AuNS)-coated wavelength-mode localized surface plasmon resonance (LSPR) fiber sensor was fabricated by a simple and time-saving electrostatic self-assembly method using poly(allylamine hydrochloride). Based on the localized enhanced coupling effect between AuNSs, the LSPR spectrums of the AuNS monolayer with good dispersity and high density exhibited a favourable capability for refractive index (RI) measurement. Based on the results obtained from the optimization for AuNS distribution, sensing length, and RI range, the best RI sensitivity of the fiber modified by 100 nm AuNS reached up to about 2975 nm/RIU, with the surrounding RI range from 1.3322 to 1.3664. Using an 80 nm AuNS-modified fiber sensor, the RI sensitivity of 3953 nm/RIU was achieved, with the RI range increased from 1.3744 to 1.3911. The effect of sensing length to RI sensitivity was proven to be negligible. Furthermore, the linear relationship between the RI sensitivity and plasma resonance frequency of the bulk metal, which was dependent on the interparticle plasmon coupling effect, was quantified. Additionally, the resonance peak was tuned from 539.18 nm to 820.48 nm by different sizes of AuNSs-coated fiber sensors at a RI of 1.3322, which means the spectrum was extended from VIS to NIR. It has enormous potential in hypersensitive biochemistry detection at VIS and NIR ranges.

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Versatile Polypeptide-Functionalized Plasmonic Paper as Synergistic Biocompatible and Antimicrobial Nanoplatform.

Nowadays, thanks to nanotechnological progress, which itself guides us more and more closely toward not only the efficient design of innovative nanomaterials or nanostructures, but to the improvement of their functionality, we benefit from an important asset in the battle against pathogenic illnesses. Herein, we report a versatile biocompatible plasmonic nanoplatform based on a Whatman paper incorporating positively-charged gold nanospherical particles via the immersion approach. The morphological characterization of the as-engineered-plasmonic paper was examined by SEM (scanning electron microscopy) and HRTEM (high-resolution transmission electron microscopy) investigations, while its surface chemical modification with a synthetic polypeptide, specifically RRWHRWWRR-NH2 (P2), was proved by monitoring the plasmonic response of loaded gold nanospheres and the emission signal of P2 via fluorescence spectroscopy. The as-functionalized plasmonic paper is non-cytotoxic towards BJ fibroblast human cells at bactericidal concentrations. Finally, the antimicrobial activity of the P2-functionalized plasmonic paper on both planktonic bacteria and biofilms was tested against two reference strains: Gram-positive Bacteria, i.e., Staphylococcus aureus and the Gram-negative Bacteria, i.e., Escherichia coli, determining microbial inhibition of up to 100% for planktonic bacteria. In line with the above presented nanoplatform's proper design, followed by their functionalization with active antimicrobial peptides, new roads can be open for determining antibiotic-free treatments against different relevant pathogens.

Colloidal Gold Nanorings and Their Plasmon Coupling with Gold Nanospheres.

Gold nanorings are attractive as plasmonic metal nanocrystals because they have a hollow inner cavity. Their enhanced electric field inside the ring cavity is accessible, which is highly desirable for assembling with other optical components and studying their plasmon-coupling behaviors. However, the lack of robust methods for synthesizing size-controllable and uniform Au nanorings severely impedes the study of their attractive plasmonic properties and plasmon-driven applications. Herein, an improved wet-chemistry method is reported for the synthesis of monodisperse colloidal Au nanorings. Using circular Au nanodisks with different thicknesses and diameters as templates, Au nanorings are synthesized with thicknesses varied from ≈30 to ≈50 nm and cavity sizes varied from ≈90 to ≈40 nm. The produced Au nanorings are assembled with colloidal Au nanospheres to yield Au nanoring-nanosphere heterodimers in sphere-in-ring and sphere-on-ring configurations on substrates. The sphere-in-ring heterodimers exhibit the interesting feature of plasmonic Fano resonance upon the excitation of the dark quadrupolar plasmon mode of the Au nanorings. The open cavity in a nanoring holds a great promise for studying plasmon-coupled systems, which will facilitate the construction of advanced metamaterials and high-performance Fano-based devices.

A semi-quantitative rapid multi-range gradient lateral flow immunoassay for procalcitonin.

A rapid semi-quantitative gradient lateral flow immunoassay (LFIA) of procalcitonin (PCT), a peptide precursor of the hormone calcitonin, was developed. The method is based on particular analyte cut-offs by immobilizing specific antibodies on the test strip with a consistent (gradient) increase in concentration from line to line. Semi-quantitative multi-range analysis is evaluated visually by counting the number of colored test lines corresponding to a certain concentration range of sepsis marker: [PCT]˂0.25; 0.25 ≤ [PCT] < 0.5; 0.5 ≤ [PCT] < 2; 2 ≤ [PCT] < 10; [PCT] ≥ 10 ng·mL-1. This multi-range gradient LFIA was implemented by using two types of label: spherical gold nanoparticles (35 nm) and hierarchical popcorn-like gold nanoparticles (100 nm). The comparison of this LFIA with an ELISA (for n = 82) yielded 87.5% and 76.6% sensitivities, and 92.3% and 92.3% specificities, respectively. Thus, multi-range gradient LFIA performs well at PCT thresholds, which is important for early diagnosis of sepsis and severe bacterial infection. In our perception, this method has a wide scope in that it may be implemented in numerous other LFIA based test systems. Graphical abstract Schematic of the gradient lateral flow immunoassay for determination of clinically relevant procalcitonin ranges. It allows to reach the correlation between the number of developed test lines and procalcitonin concentration range in serum by pre-immobilization of capture antibodies in a consistently (gradient) increasing concentration.

Gold nanospheres enhanced photothermal therapy in a rat model.

BACKGROUND AND OBJECTIVE: Efficient photothermal conversion of gold nanoparticles with strong light absorption suggests their wide use as selective photothermal agents in biomedical fields. The aim of this study is to investigate the use of gold nanospheres (GNPs) as exogenous visible light absorbers to improve laser treatment of port-wine stains. MATERIALS AND METHODS: Thiol-terminated methoxypolyethylene glycol modified GNPs (PEG-GNPs) with peak extinction matching the visible light wavelength of the laser being used were synthesized. An in vitro capillary experiment was prepared to investigate the thermal response of blood vessels with and without injection of 4.54 mg PEG-GNPs in mice prior to irradiation by a frequency-doubled Nd:YAG laser at a wavelength of 532 nm. RESULTS: The in vitro results demonstrated that the photocoagulation size in blood vessels after exposed to laser light increased with the increment of concentration of PEG-GNPs in blood within a certain range. However, the unwanted thermal response (i.e., cavitation) occurred when the concentration of PEG-GNPs in blood was larger than 2.5 mg/ml. The in vivo results suggested that more obvious blood thermal response can be induced by laser light after injection of PEG-GNPs. After injection of 4.54 mg PEG-GNPs, laser radiant exposure required for thread-like constriction of blood vessels decreased from 12.5 to 9.8 J/cm2 with the pulse duration of 10 ms, from 15 to 11.85 J/cm2 with the pulse duration of 30 ms, respectively. CONCLUSION: This in vitro and in vivo experimental results show that PEG-GNPs combined with laser light could be a promising modality to reduce the radiant exposure required for obvious blood thermal response, thereby providing a potential strategy for improving the laser treatment of cutaneous vascular lesions. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Packed hybrids of gold nanoparticles and layered double hydroxide nanosheets for microextraction of triazine herbicides from maize.

This work describes a nanohybrid material consisting of gold nanoparticles (AuNPs) and nanosheets of layered double hydroxides (NLDHs) of Mg(II) and Al(III). Mono-disperse AuNPs were immobilized on the surface of the LDHs via Au-O bonding. The nanohybrid sorbent was packed in an organic filter along with a syringe and applied to the microextraction of triazine herbicides with the help of an injection pump. The collected hexane eluate was concentrated and directly injected into a HPLC column for quantification. The effects of the amount of Au/LDH nanohydrobrids, type, flow rate, volume of washing and eluting solvent were optimized. The method was validated by detecting four triazine herbicides (prometryn, atrazine, terbumeton and secbumeton) in spiked maize. The limits of detection range between 35 and 108 pg g-1. The relative standard deviations range from 1.0-6.9% for repeatability and 4.6-7.8% for reproducibility (for n = 5). Graphical abstract Schematic presentation of a nanohybrid material consisting of gold nanoparticles and nanosheets of layered double hydroxides of Mg(II) and Al(III) (Au/LDH) for use as an adsorbent for microextraction in a packed syringe. Organic filter heads were used as the container of Au/LDHs nanohybrids, and were connected with the syringes installed on the injection pump for the semi-automatic microextraction and preconcentration of triazines in maize.

Importance of the surface chemistry of nanoparticles on peroxidase-like activity.

We report the studies on origin of peroxidase-like activity for gold nanoparticles, as well as the impact from morphology and surface charge of nanoparticles. For this purpose, we have synthesized hollow gold nanospheres (HAuNS) and gold nanorods (AuNR) with different morphology and surface chemistry to investigate their influence on the catalytic activity. We found that citrate-capped HAuNS show catalyzing efficiency in oxidation reaction of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2) and it is superior to that of cetyltrimethylammonium bromide (CTAB)-capped AuNR. The kinetics of catalytic activities from HAuNS and AuNR were respectively studied under varied temperatures. The results indicated that surface chemistry rather than morphology of nanoparticles plays an important role in the catalytic reaction of substrate. Furthermore, influencing factors such as pH, amount of nanoparticle and H2O2 concentration were also investigated on HAuNS-catalyzed system. The great impact of nanoparticle surface properties on catalytic reactions makes a paradigm in constructing nanozymes as peroxidase mimic for sensing application.

Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres.

Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases. It is found that the EphB4 receptor is overexpressed in endometriosis lesions. The data indicate that both QDs and HAuNS can efficiently accumulate in endometriotic lesions through permeable vessels and the TNYL-conjugated HAuNS (TNYL-HAuNS) accumulate more via the interaction with EphB4. The specific photothermal ablation therapy based on TNYL-HAuNS significantly inhibits the growth of the endometriotic volume and induces the atrophy and degeneration of ectopic endometrium with no detectable toxicity to the normal organs. The level of TNF-α and estradiol also significantly decreases in the endometriotic lesions, indicating that the treatment enables a recovery from hormonal imbalance and inflammatory injury. This work can be a valuable reference for future endometriosis therapy.

The effects of gold nanoparticles functionalized with ß-amyloid specific peptides on an in vitro model of blood-brain barrier.

We studied the effect of gold nanoparticle (AuNP) size, surface charge, concentration and morphology on the integrity of the blood-brain barrier (BBB) in a well-established in vitro model set-up. We focused on the effect of peptide functionalized hollow gold nanospheres and gold nanorods, which selectively bind to amyloidogenic ß-amyloid structures. These AuNP conjugates have already been successfully tested as photothermal absorbers for potential application in Alzheimer's disease (AD) therapy in an in vitro set-up, but may exhibit a low passage through the BBB due to their overall negative charge. Our results show that: (i) small (1.4 nm) AuNPs strongly affects the BBB integrity, (ii) negative surface charge impedes BBB passage, and (iii) this charge effect caused by the peptide is compensated by covalent coupling to a polyethylene glycol ligand stabilizing the particles in diluted manner.

A PCF Sensor Design Using Biocompatible PDMS for Biosensing.

A novel photonic crystal fiber (PCF) sensor for refractive index detection based on polydimethylsiloxane (PDMS) is presented in this research, as well as designs for single-channel and dual-channel structures for this PDMS-PCF sensor. The proposed structures can be used to develop sensors with biocompatible polymers. The performance of the single-channel PDMS-PCF sensor was studied, and it was found that adjusting parameters such as pore diameter, lattice constant, distance between the D-shaped structure and the fiber core, and the radius of gold nanoparticles can optimize the sensor's performance. The findings indicate that the detection range of the single-channel photonic crystal is 1.21-1.27. The maximum wavelength sensitivity is 10,000 nm/RIU with a resolution of 1×10-5 RIU, which is gained when the refractive index is set to 1.27. Based on the results of the single-channel PCF, a dual-channel PDMS-PCF sensor is designed. The refractive index detection range of the proposed sensor is 1.2-1.28. The proposed sensor has a maximum wavelength sensitivity of 13,000 nm/RIU and a maximum resolution of 7.69×10-6 RIU at a refractive index of 1.28. The designed PDMS-PCF holds tremendous potential for applications in the analysis and detection of substances in the human body in the future.

A disposable immunosensor for the detection of salivary MMP-8 as biomarker of periodontitis.

This work describes the development of a novel voltammetric immunosensor for the detection of salivary MMP-8 at the point-of-care. The electrochemical platform was based on a graphene (GPH) screen-printed electrode (SPE) functionalized by gold-nanospheres (AuNSs) and antibodies against MMP-8 protein (anti-MMP-8). The functionalization with anti-MMP-8 was realized by using 11-mercaptoundecanoic acid (11-MUA), thanks to its ability to give strong sulfur bonds with its -SH end, and to cross-link the -NH2 groups of the antibody molecule with the other -COOH end, using the traditional EDC-NHS method. The voltammetric sensor showed good performances with a linear range of 2.5-300 ng mL-1, a LOD value of 1.0 ± 0.1 ng mL-1 and a sensitivity of 0.05 µA mL cm-2 ng-1. Moreover, the proposed immunosensor was tested in real saliva samples, showing comparable results to those obtained with the conventional ELISA method. The biosensor was single-use and cost-effective and required a small quantity of test medium and a short preparation time, representing a very attractive biosensor for MMP-8 detection in human saliva.

Au nanodyes as enhanced contrast agents in wide field near infrared fluorescence lifetime imaging.

The near-infrared (NIR) range of the electromagnetic (EM) spectrum offers a nearly transparent window for imaging tissue. Despite the significant potential of NIR fluorescence-based imaging, its establishment in basic research and clinical applications remains limited due to the scarcity of fluorescent molecules with absorption and emission properties in the NIR region, especially those suitable for biological applications. In this study, we present a novel approach by combining the widely used IRdye 800NHS fluorophore with gold nanospheres (GNSs) and gold nanorods (GNRs) to create Au nanodyes, with improved quantum yield (QY) and distinct lifetimes. These nanodyes exhibit varying photophysical properties due to the differences in the separation distance between the dye and the gold nanoparticles (GNP). Leveraging a rapid and highly sensitive wide-field fluorescence lifetime imaging (FLI) macroscopic set up, along with phasor based analysis, we introduce multiplexing capabilities for the Au nanodyes. Our approach showcases the ability to differentiate between NIR dyes with very similar, short lifetimes within a single image, using the combination of Au nanodyes and wide-field FLI. Furthermore, we demonstrate the uptake of Au nanodyes by mineral-oil induced plasmacytomas (MOPC315.bm) cells, indicating their potential for in vitro and in vivo applications.

An ultra pH-sensitive and aptamer-equipped nanoscale drug-delivery system for selective killing of tumor cells.

Nanotechnology has often been applied in the development of targeted drug-delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off-target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker-specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt-HAuNS-Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer-mediated selective cell binding, the Apt-HAuNS-Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt-HAuNS-Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt-HAuNS-Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off-target cells in the same cultures, indicating that this ultra pH-sensitive Apt-HAuNS-Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue.

A novel gold-polymer-antibody conjugate for targeted (radio-photothermal) treatment of HepG2 cells.

Localization of the near-infrared (NIR) plasmonic nanoparticles at the tumor sites is essential for safe and efficient photothermal therapy of cancer. In this work, two biocompatible polymers: modified poly(ethylene glycol) (PEG) and branched polyethyleneimine (bPEI) were used to bind plasmonic hollow gold nanospheres (HAuNS) to the tumor-specific antibody, atezolizumab (ATZ). The photo-immunoconjugate (HAuNS-PEI-PEG-ATZ) was prepared via a simple and cost-effective procedure. The conjugate was also prepared with the radioiodinated antibody (ATZ-131I) to combine the targeted radio- and photothermal cytotoxic actions against human hepatoma (HepG2) cells. In vitro study revealed that attachment to the antibody and the use of cellular internalizing polymers enhanced the cellular localization of both gold and the radiotherapeutic Iodine-131. Compared to bare gold nanoparticles, (HAuNS-PEI-PEG-ATZ) conjugate exhibited a significantly enhanced photothermal ablation of HepG2 cells after laser irradiation (0.4 W cm-2, 5 min). Laser irradiation of the cells treated with the radiolabeled conjugate (HAuNS-PEI-PEG-ATZ-131I) exhibited the highest cytotoxicity against HepG2 cells due to the combinatorial cytotoxic effects.

Gold nanoparticles combined baker's yeast as a successful approach for breast cancer treatment.

BACKGROUND: Saccharomyces cerevisiae (S. cerevisiae) has been demonstrated in vitro to sensitize several breast cancer cell lines and to be a safe, non-toxic drug with anti-skin cancer action in mice. Furthermore, plasmonic photothermal treatment using gold nanorods has been authorized as a novel method for in vitro and in vivo cancer therapy. RESULTS: When compared to tumor-free rats, the treatment with S. cerevisiae conjugated to gold nanospheres (GNSs) lowered Bcl-2 levels while increasing FasL, Bax, cytochrome c, and caspases 8, 9, and 3 levels. Histopathological results showed changes reflecting the ability of nanogold conjugated heat-killed yeast to induce apoptosis is greater than heat-killed yeast alone as the nanogold conjugated with heat-killed yeast showed no tumor, no hyperplasia, no granulation tissue formation, no ulceration, and no suppuration. Nanogold conjugated with heat-killed yeast-treated breast cancer group displayed normal levels of ALT and AST, indicating relatively healthy hepatic cells. CONCLUSION: Our results proved that nanogold conjugated heat-killed yeast can initiate apoptosis and can be used as a safe non-invasive method for breast cancer treatment more effectively than the yeast alone. This, in turn, gives us new insight and a future hope for the first time that breast cancer can be treated by non-invasive, simple, safe, and naturally originated method and achieves a hopeful treatment and a novel method for in vivo cancer therapy.

Morphologic design of nanogold carriers for a carbonic anhydrase inhibitor: Effect on ocular retention and intraocular pressure.

Morphologic design of nanomaterials for a diversity of biomedical applications is of increasing interest. The aim of the current study is to construct therapeutic gold nanoparticles of different morphologies and investigate their effect on ocular retention and intraocular pressure in a glaucoma rabbit model. Poly(lactic-co-glycolic acid) (PLGA)-coated nanorods and nanospheres have been synthesized and loaded with carbonic anhydrase inhibitor (CAI), and characterized in vitro for their size, zeta potential and encapsulation efficiency. Nanosized PLGA-coated gold nanoparticles of both morphologies demonstrated high entrapment efficiency (˃ 98%) for the synthesized CAI and the encapsulation of the drug into the developed nanoparticles was confirmed via Fourier transform-infrared spectroscopy. In vivo studies revealed a significant reduction in intraocular pressure upon instillation of drug-loaded nanogold formulations compared to the marketed eye drops. Spherical nanogolds exhibited a superior efficacy compared to the rod-shaped counterparts, probably due to the enhanced ocular retention of spherical nanogolds within collagen fibers of the stroma, as illustrated by transmission electron microscopy imaging. Normal histological appearance was observed for the cornea and retina of the eyes treated with spherical drug-loaded nanogolds. Hence, incorporation of a molecularly-designed CAI into nanogold of tailored morphology may provide a promising strategy for management of glaucoma.