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With several gold nanoparticle-based therapies currently undergoing clinical trials, these treatments may soon be in the clinic as novel anticancer agents. Gold nanoparticles are the subject of a wide ranging international research effort with preclinical studies underway for multiple applications including photoablation, diagnostic imaging, radiosensitization and multifunctional drug-delivery vehicles. These applications require an increasingly complex level of surface modification in order to achieve efficacy and limit off-target toxicity. This review will discuss the main obstacles in relation to surface functionalization and the chemical approaches commonly utilized. Finally, we review a range of recent preclinical studies that aim to advance gold nanoparticle treatments toward the clinic.

Background New vaccines with broader protection against SARS-CoV-2 are needed to reduce the risk of immune escape and provide broad and long-lasting cellular immunity. The objectives of the naNO-COVID trial were to evaluate the safety and immunogenicity of a CD8 + T cell, gold nanoparticle-based, peptide COVID-19 vaccine. Methods A randomized, double-blind, vehicle-controlled, phase 1 trial in healthy adults to receive PepGNP-Covid19 or Vehicle-GNP, followed over 180 days, using a dose-escalation strategy. Results Twenty participants received PepGNP-Covid19 (low dose [LD] or high dose [HD], n  = 10 each) and six Vehicle-GNP (LD or HD, n  = 3 each). Vaccinations were safe. No serious adverse events were reported. Most of the adverse events were mild, two adverse events of special interest related to the product (fever and fatigue). Reactogenicity was similar overall between vaccine, comparator, and doses. Virus-specific humoral responses in LD PepGNP-Covid19 and Vehicle-GNP groups coincided with SARS-CoV-2 infections. PepGNP-Covid19 vaccination induced the modulation of Covid19-specific CD137 + CD69 + CD8 + , and an increase at day 35 particularly in central and effector memory T cells in LD group, and in late effector memory cells in HD group. Conclusions The favourable safety profile and cellular responses observed support further development of PepGNP-Covid19. Trial registration ClinicalTrials.gov, NCT05113862, approved 09.11.2021.

Silver nanoparticles (AgNPs) have now been recognized as promising therapeutic molecules and are extending their use in cancer diagnosis and therapy. This study demonstrates for the first time the antitumor activity of green-synthesized AgNPs against lung cancer in vitro and in vivo. Cytotoxicity effect was explored on human lung cancer H1299 cells in vitro by MTT and trypan blue assays. Apoptosis was measured by morphological assessment, and nuclear factor-κB (NF-κB) transcriptional activity was determined by a luciferase reporter gene assay. The expressions of phosphorylated stat3, bcl-2, survivin, and caspase-3 were examined by Western blot analysis. AgNPs showed dose-dependent cytotoxicity and stimulation of apoptosis in H1299 cells. The effects on H1299 cells correlated well with the inhibition of NF-κB activity, a decrease in bcl-2, and an increase in caspase-3 and survivin expression. AgNPs significantly suppressed the H1299 tumor growth in a xenograft severe combined immunodeficient (SCID) mouse model. The results demonstrate the anticancer activities of AgNPs, suggesting that they may act as potential beneficial molecules in lung cancer chemoprevention and chemotherapy, especially for early-stage intervention.

Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules.

Paclitaxel is a generic drug produced based on Taxol which is an extract of tree, well known for its anticancer and antibacterial effects. This study was aimed at building up an agent with the antibacterial and anticancer benefits of both the silver ions and Taxol, together with less cytotoxic effects. Colloidal silver nanoparticles (AgNPs) were synthesized by reducing aqueous AgNO with aqueous leaf extract at nonphotomediated conditions, without any catalyst, template or surfactant. The AgNP production was confirmed by ultraviolet-visible (UV-VIS) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier-transform infrared (FTI) spectroscopy. The MTT assay for human breast cancer cells as well as the DAPI fluorescent staining microscopy tested the biocompatibility and anticancer effects of AgNPs, silver nitrate, and Taxol. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques were performed to determine the shape and size of the nanoparticles. MTT assay showed the best inhibitory concentration of AgNPs on cancer cells. The antibacterial activity of the three case study materials was tested for gram-positive ( ) and gram-negative bacteria ( and ) using well diffusion test. This work proposes more anticancer effects for AgNP made by extract, comparing Taxol solution. IC50 was observed as 3.1 mM for Taxol while 1.5 mM for new AgNP. Moreover, showed no antibacterial effects while the new AgNP showed a dose-dependent biocompatibility along with slightly more antibacterial effects (MIC: 1.6 and 6.6mM for gram-positive and -negative bacteria, respectively) comparing with silver nitrate solution (MIC: 1.5 and 6.2 mM for gram-positive and -negative bacteria, respectively). The production of herbal-mediated silver nanoparticles may be an efficient substitution for the silver nitrate-based medicines with less side effects.

We conducted inhalation and intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

Gastric cancer is the fourth most common cancer and second leading cause of cancer death worldwide. is used to treat nerve disorders, stiffness, rheumatism, ear ache, snake bite, and so on. In this study, the reaction parameters were optimized to control the size of the nanoparticle, which was confirmed by transmission electron microscopy. Various characterization techniques such as selected area diffraction pattern, UV-visible spectroscopy, energy-dispersive X-ray analysis, dynamic light scattering, Fourier-transform infrared spectroscopy, and atomic force microscopy were employed to analyze the synthesized AuNPs obtained from (CH-AuNP) against gastric carcinoma cell line. The cytotoxic effect of CH-AuNP against AGS, SNU-5, and SNU-16 cell lines was detected by MTT assay. The induction of apoptosis by CH-AuNP in AGS was analyzed by double staining technique using TUNEL and DAPI staining assays. Further to confirm the molecular mechanism exhibited by CH-AuNP to induce apoptosis, the intracellular ROS level was assessed and immunoblotting was performed to assess the apoptotic signaling molecules that often deregulated in cancerous condition. The results clearly prove that CH-AuNP increases ROS and induces apoptosis in AGS, suggesting that CH-AuNP may be an effective anticancer drug with no side effects to treat gastric cancer.

The production and demand of nanoparticles in the manufacturing sector and personal care products, release a large number of engineered nanoparticles (ENPs) into the atmosphere, aquatic ecosystems, and terrestrial environments. The intentional or involuntary incorporation of ENPs into the environment is carried out through different processes. The ENPs are combined with other compounds and release into the atmosphere, settling on the ground due to the water cycle or other atmospheric phenomena. In the case of aquatic ecosystems, the ENPs undergo hetero-aggregation and sedimentation, reaching different living organisms and flora, as well as groundwater. Accordingly, the high mobility of ENPs in diverse ecosystems is strongly related to physical, chemical, and biological processes. Recent studies have been focused on the toxicological effects of a wide variety of ENPs using different validated biological models. This literature review emphasizes the study of toxicological effects related to using the most common ENPs, specifically metal and metal/oxides-based nanoparticles, addressing different synthesis methodologies, applications, and toxicological evaluations. The results suggest negative impacts on biological models, such as oxidative stress, metabolic and locomotive toxicity, DNA replication dysfunction, and bioaccumulation. Finally, it was consulted the protocols for the control of risks, following the assessment and management process, as well as the classification system for technological alternatives and risk management measures of ENPs, which are useful for the transfer of technology and nanoparticles commercialization.

Nanotechnology is constantly expanding, with nanomaterials being more and more used in common commercial products that define our modern life. Among all types of nanomaterials, nanoparticles (NPs) occupy an important place, considering the great amount that is produced nowadays and the diversity of their applications. Conventional techniques applied to synthesize NPs have some issues that impede them from being appreciated as safe for the environment and health. The alternative to these might be the use of living organisms or biological extracts that can be involved in the green approach synthesis of NPs, a process that is free of harmful chemicals, cost-effective and a low energy consumer. Several factors, including biological reducing agent concentration, initial precursor salt concentration, agitation, reaction time, pH, temperature and light, can influence the characteristics of biologically synthesized NPs. The interdependence between these reaction parameters was not explored, being the main impediment in the implementation of the biological method on an industrial scale. Our aim is to present a brief review that focuses on the current knowledge regarding how the aforementioned factors can control the size and shape of green-synthesized NPs. We also provide an overview of the biomolecules that were found to be suitable for NP synthesis. This work is meant to be a support for researchers who intend to develop new green approaches for the synthesis of NPs.