Targeted photodynamic therapy technique of Janus nanoparticles on breast cancer.

Spherical gold/polyacrylic acid (Au/PAA) polymer-inorganic Janus nanoparticles (JNPs) with simultaneous therapeutic and targeting functions were fabricated. The obtained Au/PAA JNPs were further selectively functionalized with folic acid (FA) and thiol PEG amine (SH-PEG-NH2) on Au sides to provide superior biocompatibility and active targeting, while the other PAA sides were loaded with 5-aminolevulinic acid (5-ALA) to serve as a photosensitizer (PS) for photodynamic therapeutic (PDT) effects on MCF-7 cancer cells. The PS loading of 5-ALA was found to be 83% with an average hydrodynamic size and z-potential of 146 ± 0.8 nm and -6.40 mV respectively for FA-Au/PAA-ALA JNPs. The in vitro PDT study of the JNPs on MCF-7 breast cancer cells under 636 nm laser irradiation indicated the cell viability of 24.7% ± 0.5 for FA-Au/PAA-ALA JNPs at the IC50 value of 0.125 mM. In this regard, the actively targeted FA-Au/PAA-ALA JNPs treatment holds great potential for tumour therapy with high cancer cell-killing efficacy.

Induction of autophagy-dependent and caspase- and microtubule-acetylation-independent cell death by phytochemical-stabilized gold nanopolygons in colorectal adenocarcinoma cells.

Collective functionalization of the phytochemicals of medicinal herbs on nanoparticles is emerging as a potential cancer therapeutic strategy. This study presents the facile synthesis of surface-functionalized gold nanoparticles using Bacopa monnieri (Brahmi; Bm) phytochemicals and their therapeutically relevant mechanism of action in the colorectal cancer cell line, HT29. The nanoparticles were characterized using UV-visible spectroscopy, TEM-EDAX, zeta potential analysis, TGA, FTIR and 1H NMR spectroscopy, and HR-LC-MS. The particles (Bm-GNPs) were of polygonal shape and were stable against aggregation. They entered the target cells and inhibited the viability and clonogenicity of the cells with eight times more antiproliferative efficacy (25 ± 1.5 µg mL-1) than Bm extract (Bm-EX). In vitro studies revealed that Bm-GNPs bind tubulin (a protein crucial in cell division and a target of anticancer drugs) and disrupt its helical structure without grossly altering its tertiary conformation. Like other antitubulin agents, Bm-GNPs induced G2/M arrest and ultimately killed the cells, as confirmed using flow cytometry analyses. ZVAD-FMK-mediated global pan-caspase inhibition and the apparent absence of cleaved caspase-3 in treated cells indicated that the death did not involve the classic apoptosis pathway. Cellular ultrastructure analyses, western immunoblots, and in situ immunofluorescence visualization of cellular microtubules revealed microtubule-acetylation-independent induction of autophagy as the facilitator of cell death. Together, the data indicate strong antiproliferative efficacy and a possible mechanism of action for these designer nanoparticles. Bm-GNPs, therefore, merit further investigations, including preclinical evaluations, for their therapeutic potential as inducers of non-apoptotic cell death.

Anticancer photodynamic activities of triphenylphosphine-labelled phthalocyanines and their bovine serum albumin-gold nanoparticles- complexes on melanoma A375 cell lines in vitro.

This work reports on the synthesis of triphenylphosphine-labelled cationic phthalocyanines (Pc) complexed with bovine serum albumin (BSA) and gold nanoparticles (Au NPs). This nano-complex (Pc-BSA-Au) is studied for its photodynamic therapy (PDT) activity compared to the non-complexed Pc counterpart. The photochemical properties and in vitro PDT efficacies of the Pc and the nano-complex were determined and are compared herein. The singlet oxygen (1O2) yields of the Pcs were determined and are reported in DMF. A singlet oxygen quantum yield of 0.47 was obtained for the Pcs. The PDT efficacies of the complexes were thereafter determined using malignant melanoma A375 cancer cell line in vitro. An increase in the cell toxicity was observed for cells treated with Pc-BSA-Au compared to those treated with the Pc alone. The cell survival percentages were 23.1% for cells treated with Pc-BSA-Au and 48.7% for those treated with Pc alone under PDT treatments.

Bionic nanotheranostic for multimodal imaging-guided NIR-II-photothermal cancer therapy.

In photothermal therapy (PTT), the photothermal conversion of the second near-infrared (NIR-II) window allows deeper penetration and higher laser irradiance and is considered a promising therapeutic strategy for deep tissues. Since cancer remains a leading cause of deaths worldwide, despite the numerous treatment options, we aimed to develop an improved bionic nanotheranostic for combined imaging and photothermal cancer therapy. We combined a gold nanobipyramid (Au NBP) as a photothermal agent and MnO2 as a magnetic resonance enhancer to produce core/shell structures (Au@MnO2; AM) and modified their surfaces with homologous cancer cell plasma membranes (PM) to enable tumour targeting. The performance of the resulting Au@MnO2@PM (AMP) nanotheranostic was evaluated in vitro and in vivo. AMP exhibits photothermal properties under NIR-II laser irradiation and has multimodal in vitro imaging functions. AMP enables the computed tomography (CT), photothermal imaging (PTI), and magnetic resonance imaging (MRI) of tumours. In particular, AMP exhibited a remarkable PTT effect on cancer cells in vitro and inhibited tumour cell growth under 1064 nm laser irradiation in vivo, with no significant systemic toxicity. This study achieved tumour therapy guided by multimodal imaging, thereby demonstrating a novel strategy for the use of bionic gold nanoparticles for tumour PTT under NIR-II laser irradiation.

Improved Immune Response for Colorectal Cancer Therapy Triggered by Multifunctional Nanocomposites with Self-Amplifying Antitumor Ferroptosis.

Ferroptosis, as a type of regulated cell death, can trigger the release of damage-associated molecular patterns from cancer cells and lead to the enhancement of immune recognition. Fenton reaction-mediated chemodynamic therapy could initiate ferroptosis by generating lipid peroxides, but its efficiency would be greatly restricted by the insufficient H2O2 and antioxidant system within the tumor. Herein, this work reports the successful preparation of H2O2 self-supplied and glutathione (GSH)-depletion therapeutic nanocomposites (Cu2O@Au) through in situ growth of Au nanoparticles on the surface of cuprous oxide (Cu2O) nanospheres. Upon delivery into cancer cells, the released Cu2O could consume endogenous H2S within colorectal cancer cells to form Cu31S16 nanoparticles, while the released Au NPs could catalyze glucose to generate H2O2 and gluconic acid. The self-supplying endogenous H2O2 and lower acidity could amplify the Cu ion-induced Fenton-like reaction. Meanwhile, the consumption of glucose would reduce GSH generation by disrupting the pentose phosphate pathway. Additionally, the Cu2+/Cu+ catalytic cycle promotes the depletion of GSH, leading to lipid peroxide accumulation and ferroptosis. It was found that the onset of ferroptosis triggered by Cu2O@Au could initiate immunologic cell death, promote dendritic cell maturation and T-cell infiltration, and finally enhance the antitumor efficacy of the PD-L1 antibody. In summary, this collaborative action produces a remarkable antitumor effect, which provides a promising treatment strategy for colorectal cancer.

"Four-in-One" Nanozyme for Amplified Catalytic-Photothermal Therapy.

The cancer therapeutic efficacy of the peroxidase (POD)-mimicking nanozyme-based monotherapy is significantly hindered due to insufficient intratumoral hydrogen peroxide (H2O2) and glutathione (GSH) consumption effect on reactive oxygen species (ROS). In this study, we present the development of poly(o-phenylenediamine)@gold nanoparticles (AuNPs) (PoPD@Au) nanocomposites for multifunctional catalytic-photothermal therapy. These nanocomposites exhibit triple distinct nanozymatic activities, i.e., POD-like activity that catalyzes H2O2 to ROS, glucose oxidase (GOx)-like activity that supplements endogenous H2O2, and GSH depleting activity that decreases the ROS consumption efficiency. This open source and reduce expenditure strategy for ROS generation allows for the amplification of tumor oxidative stress, thereby enhancing anti-tumor efficiency. Additionally, the PoPD@Au nanocomposites demonstrate outstanding photothermal conversion efficiency, contributing to the synergistic effect between PoPD and AuNPs. Moreover, we reveal the improved photothermal performance of PoPD@Au triggered by the tumor microenvironment pH, which provides additional benefits for targeted catalytic-photothermal therapy. This "four-in-one" design of PoPD@Au enables efficient anti-tumor effects both in vitro and in vivo, making it a universal strategy for engineering catalytic-photothermal therapeutic nanoagents.

Clonogenic assay and computational modeling using real cell images to study physical enhancement and cellular sensitization induced by metal nanoparticles under MV and kV X-ray irradiation.

This study was initiated due to the physically unexplainable tumor controls resulting from metal nanoparticle (MNP) experiments even under MV X-ray irradiation. A more accurate explanation of the mechanism of radiosensitization induced by MNP is warranted, considering both its physical dose enhancement and biological sensitization, as related research is lacking. Thus, we aimed to examine the intricate dynamics involved in MNP-induced radiosensitization. We conducted specifically designed clonogenic assays for the A549 lung cancer cell line with MNP irradiated by 6 MV and 300 kVp X-rays. Two types of MNP were employed: one based on iron oxide, promoting ferroptosis, and the other on gold nanoparticles known for inducing a significant dose enhancement, particularly at low-energy X-rays. We introduced the lethality enhancement factor (LEF) as the fraction in the cell killing attributed to biological sensitization. Subsequently, Monte Carlo simulations were conducted to evaluate the radial dose profiles for each MNP, corresponding to the physical enhancement. Finally, the local effect model was applied to the clonogenic assay results on real cell images. The LEF and the dose enhancement in the cytoplasm were incorporated to increase the accuracy in the average lethal events and, consequently, in the survival fraction. The results reveal an increased cell killing for both of the MNP under MV and kV X-ray irradiation. In both types of MNP, the LEF reveals a biological sensitization evident. The sensitizer enhancement ratio, derived from the calculations, exhibited only 3% and 1% relative differences compared to the conventional linear-quadratic model for gold and ferroptosis inducer nanoparticles, respectively. These findings indicate that MNPs sensitize cells via radiation through mechanisms akin to ferroptosis inducers, not exclusively relying on a physical dose enhancement. Their own contributions to survival fractions were successfully integrated into computational modeling.

Bioengineered amyloid peptide for rapid screening of inhibitors against main protease of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has evoked a worldwide pandemic. As the emergence of variants has hampered the neutralization capacity of currently available vaccines, developing effective antiviral therapeutics against SARS-CoV-2 and its variants becomes a significant challenge. The main protease (Mpro) of SARS-CoV-2 has received increased attention as an attractive pharmaceutical target because of its pivotal role in viral replication and proliferation. Here, we generated a de novo Mpro-inhibitor screening platform to evaluate the efficacies of Mpro inhibitors based on Mpro cleavage site-embedded amyloid peptide (MCAP)-coated gold nanoparticles (MCAP-AuNPs). We fabricated MCAPs comprising an amyloid-forming sequence and Mpro-cleavage sequence, mimicking in vivo viral replication process mediated by Mpro. By measuring the proteolytic activity of Mpro and the inhibitory efficacies of various drugs, we confirmed that the MCAP-AuNP-based platform was suitable for rapid screening potential of Mpro inhibitors. These results demonstrated that our MCAP-AuNP-based platform has great potential for discovering Mpro inhibitors and may accelerate the development of therapeutics against COVID-19.

Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation.

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

NIR-Active Gold Dogbone Nanorattles Impregnated in Cationic Dextrin Nanoparticles for Cancer Nanotheranostics.

Theranostic systems, which integrate therapy and diagnosis into a single platform, have gained significant attention as a promising approach for noninvasive cancer treatment. The field of image-guided therapy has revolutionized real-time tumor detection, and within this domain, plasmonic nanostructures have garnered significant attention. These structures possess unique localized surface plasmon resonance (LSPR), allowing for enhanced absorption in the near-infrared (NIR) range. By leveraging the heat generated from plasmonic nanoparticles upon NIR irradiation, target cancer cells can be effectively eradicated. This study introduces a plasmonic gold dogbone-nanorattle (AuDB NRT) structure that exhibits broad absorption in the NIR region and demonstrates a photothermal conversion efficiency of 35.29%. When exposed to an NIR laser, the AuDB NRTs generate heat, achieving a maximum temperature rise of 38 °C at a concentration of 200 µg/mL and a laser power density of 3 W/cm2. Additionally, the AuDB NRTs possess intrinsic electromagnetic hotspots that amplify the signal of a Raman reporter molecule, making them an excellent probe for surface-enhanced Raman scattering-based bioimaging of cancer cells. To improve the biocompatibility of the nanorattles, the AuDB NRTs were conjugated with mPEG-thiol and successfully encapsulated into cationic dextrin nanoparticles (CD NPs). Biocompatibility tests were performed on HEK 293 A and MCF-7 cell lines, revealing high cell viability when exposed to AuDB NRT-CD NPs. Remarkably, even at a low laser power density of 1 W/cm2, the application of the NIR laser resulted in a remarkable 80% cell death in cells treated with a nanocomposite concentration of 100 µg/mL. Further investigation elucidated that the cell death induced by photothermal heat followed an apoptotic mechanism. Overall, our findings highlight the significant potential of the prepared nanocomposite for cancer theranostics, combining effective photothermal therapy along with the ability to image cancer cells.

Antimicrobial peptide mimetic minimalistic approach leads to very short peptide amphiphiles-gold nanostructures for potent antibacterial activity.

Strategically controlling concentrations of lipid-conjugated L-tryptophan (vsPA) guides the self-assembly of nanostructures, transitioning from nanorods to fibres and culminating in spherical shapes. The resulting Peptide-Au hybrids, exhibiting size-controlled 1D, 2D, and 3D nanostructures, show potential in antibacterial applications. Their high biocompatibility, favourable surface area-to-volume ratio, and plasmonic properties contribute to their effectiveness against clinically relevant bacteria. This controlled approach not only yields diverse nanostructures but also holds promise for applications in antibacterial therapeutics.

Treatment of dental biofilm-forming bacterium Streptococcus mutans using tannic acid-mediated gold nanoparticles.

Biosynthesized gold nanoparticles (AuNPs) are highly attracted as a biocompatible nanodrug to treat various diseased conditions in humans. In this study, phytochemical tannic acid-mediated AuNPs (TA-AuNPs) are successfully synthesized and tested for antibacterial and antibiofilm activity against dental biofilm-forming Streptococcus mutans biofilm. The synthesized TA-AuNPs are appeared as spherical in shape with an average size of 19 nm. The antibacterial potential of TA-AuNPs was evaluated using ZOI and MIC measurements; while, antibiofilm efficacy was measured by checking the eradication of preformed biofilm on the tooth model. The ZOI and MIC values for TA-AuNPs are 25 mm in diameter and 4 µg/mL, respectively. The MTT assay, CLSM, and SEM results demonstrate that the preformed S. mutans biofilm is completely eradicated at 4xMIC (16 µg/mL) of TA-AuNPs. Finally, the present study reveals that the synthesized TA-AuNPs might be a great therapeutic drug to treat dental biofilm-forming bacterium S. mutans.

Nel-like Molecule Type 1 Combined with Gold Nanoparticles Modulates Macrophage Polarization, Osteoclastogenesis, and Oral Microbiota in Periodontitis.

The disruption of host-microbe homeostasis and uncontrolled inflammatory response have been considered as vital causes for developing periodontitis, subsequently leading to an imbalance between the bone and immune system and the collapse of bone homeostasis. Consequently, strategies to modulate the immune response and bone metabolization have become a promising approach to prevent and treat periodontitis. In this study, we investigated the cooperative effects of Nel-like molecule type 1 (Nell-1) and gold nanoparticles (AuNPs) on macrophage polarization, osteoclast differentiation, and the corresponding functions in an experimental model of periodontitis in rats. Nell-1-combined AuNPs in in vitro studies were found to reduce the production of inflammatory factors (TNF-α, p < 0.0001; IL-6, p = 0.0012), modulate the ratio of M2/M1 macrophages by inducing macrophage polarization into the M2 phenotype, and inhibit cell fusion, maturation, and activity of osteoclasts. Furthermore, the local application of Nell-1-combined AuNPs in in vivo studies resulted in alleviation of damages to the periodontal and bone tissues, modulation of macrophage polarization and the activity of osteoclasts, and alteration of the periodontal microbiota, in which the relative abundance of the probiotic Bifidobacterium increased (p < 0.05). These findings reveal that Nell-1-combined AuNPs could be a promising drug candidate for the prevention and treatment of periodontitis. However, Nell-1-combined AuNPs did not show organ toxicity or impair the integrity of intestinal epithelium but alter the gut microbiota, leading to the dysbiosis of gut microbiota. The adverse impact of changes in gut microbiota needs to be further investigated. Nonetheless, this study provides a novel perspective and direction for the biological safety assessment of biomaterials in oral clinical applications.

Gold nanoparticles (AuNPs) decrease the viability of cervical cancer cells by inducing the BAX gene and activating antioxidant enzymes.

BACKGROUND: Cervical Cancer (CC), a leading cause of female mortality worldwide, demonstrates a direct association with high-risk human papillomavirus (HPV) infections. However, not all CC patients exhibit HPV infection, suggesting additional predisposing factors. Recently, disturbances in the oxidant-antioxidant balance have been implicated in CC development. This study explores the impact of gold nanoparticles (AuNPs) on the survival and antioxidant capacity of HeLa cells, aiming to contribute to novel CC therapy approaches. METHODS AND RESULTS: Synthesized and characterized AuNPs (25.5 nm, uniform distribution according to the DLS analysis) were administered to HeLa cells at varying concentrations. After 24 h, cell viability was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide) (MTT) assay. Real-time PCR measured expression levels of apoptosis-related genes (BCL2 associated X (BAX) and p53). Catalase and superoxide dismutase (SOD) activities, key antioxidant enzymes, were also evaluated post-AuNP treatment. AuNPs dose-dependently reduced HeLa cell viability, with an IC50 value of 113 µg/ml. BAX gene expression significantly increased, indicating pro-apoptotic effects. Moreover, enzyme activities significantly rose under AuNP influence. CONCLUSIONS: AuNPs demonstrated the potential to induce HeLa cell death by upregulating pro-apoptotic BAX gene expression and altering antioxidant system enzyme activities. These findings underscore the promise of AuNPs as a therapeutic avenue for CC, emphasizing their impact on crucial cellular processes involved in cancer progression.

Size Dependence of Gold Nanorods for Efficient and Rapid Photothermal Therapy.

In recent years, gold nanomaterials have become a hot topic in photothermal tumor therapy due to their unique surface plasmon resonance characteristics. The effectiveness of photothermal therapy is highly dependent on the shape and size of gold nanoparticles. In this work, we investigate the photothermal therapeutic effects of four different sizes of gold nanorods (GNRs). The results show that the uptake of short GNRs with aspect ratios 3.3-3.5 by cells is higher than that of GNRs with aspect ratios 4-5.5. Using a laser with single pulse energy as low as 28 pJ laser for 20 s can induce the death of liver cancer cells co-cultured with short GNRs. Long GNRs required twice the energy to achieve the same therapeutic effect. The dual-temperature model is used to simulate the photothermal response of intracellular clusters irradiated by a laser. It is found that small GNRs are easier to compact because of their morphological characteristics, and the electromagnetic coupling between GNRs is better, which increases the internal field enhancement, resulting in higher local temperature. Compared with a single GNR, GNR clusters are less dependent on polarization and wavelength, which is more conducive to the flexible selection of excitation laser sources.

New retinoblastoma (RB) drug delivery approaches: anti-tumor effect of atrial natriuretic peptide (ANP)-conjugated hyaluronic-acid-coated gold nanoparticles for intraocular treatment of chemoresistant RB.

Intraocular drug delivery is a promising approach for treatment of ocular diseases. Chemotherapeutic drugs used in retinoblastoma (RB) treatment often lead to side effects and drug resistances. Therefore, new adjuvant therapies are needed to treat chemoresistant RBs. Biocompatible gold nanoparticles (GNPs) have unique antiangiogenic properties and can inhibit cancer progression. The combination of gold and low-molecular-weight hyaluronan (HA) enhances the stability of GNPs and promotes the distribution across ocular barriers. Attached to HA-GNPs, the atrial natriuretic peptide (ANP), which diminishes neovascularization in the eye, is a promising new therapeutic agent for RB treatment. In the study presented, we established ANP-coupled HA-GNPs and investigated their effect on the tumor formation potential of chemoresistant RB cells in an in ovo chicken chorioallantoic membrane model and an orthotopic in vivo RB rat eye model. Treatment of etoposide-resistant RB cells with ANP-HA-GNPs in ovo resulted in significantly reduced tumor growth and angiogenesis compared with controls. The antitumorigenic effect could be verified in the rat eye model, including a noninvasive application form via eye drops. Our data suggest that ANP-HA-GNPs represent a new minimally invasive, adjuvant treatment option for RB.

Synergistic Combination of an Intelligent Nanozyme and Radiotherapy for Treating Renal Cancer.

Background: Preserving nephrons while avoiding tumor recurrence during the treatment of renal cell carcinoma remains as a challenge in clinic. To achieve desired therapeutic outcome, we developed specific nanozymes based on the tumor microenvironment and evaluated its efficacy in combination with radiotherapy. Methods: Herein, a hybrid nanozyme CeO2@Au-PEG nanocomposite nanoparticle (NPs) was developed for the treatment of renal tumor. It was composed of gold nanozyme decorated CeO2 nanorods and exhibited both glucose-oxidase like by gold nanozyme and peroxidase-like catalytic activities. Due to the high metabolic rate of tumor cells, they take up a huge amount of glucose to survive and proliferate. Therefore, we generated CeO2@Au-PEG NPs, which exhausted glucose in the tumor tissue and generated hydrogen peroxide, depleting the source of energy and causing tumor cell death. Then the generated hydrogen peroxide was degraded by the peroxidase-mimicking properties of CeO2@Au-PEG NPs, elevating oxidative stress and thus enhancing tumor cell death. Moreover, due to the high mass nuclei of gold and cerium, they could further sensitize the tumors to radiotherapy and thus thoroughly eliminate tumors. Results: With enough biocompatibility, CeO2@Au-PEG NPs showed superior ability to deplete glucose as well as enhance oxidative stress by producing reactive oxygen species in RENCA cells under ionizing irradiation. Moreover, CeO2@Au-PEG NPs greatly improved radiotherapy mediated tumor ablation in tumor bearing mice. Conclusion: Systematic experiments demonstrated the synergistic therapeutic effects of the combination of CeO2@Au-PEG NPs and radiotherapy in renal tumor model, which may serve as a promising strategy for treating renal cancer patients in the clinic.

Radioactive gold nanoparticles coated with BSA: A promising approach for prostate cancer treatment.

Background: Nanotechnology has revolutionized medicine, especially in oncological treatments. Gold nanoparticles (AuNPs) stand out as an innovative alternative due to their biocompatibility, potential for surface modification, and effectiveness in radiotherapeutic techniques. Given that prostate cancer ranks as one of the leading malignancies among men, there's a pressing need to investigate new therapeutic approaches. Methods: AuNPs coated with bovine serum albumin (BSA) were synthesized and their cytotoxicity was assessed against prostate tumor cell lines (LNCaP and PC-3), healthy prostate cells (RWPE-1), and endothelial control cells (HUVEC) using the MTS/PMS assay. For in vivo studies, BALB/C Nude mice were employed to gauge the therapeutic efficacy, biodistribution, and hematological implications post-treatment with BSA-coated AuNPs. Results: The BSA-coated AuNPs exhibited cytotoxic potential against PC-3 and LNCaP lines, while interactions with RWPE-1 and HUVEC remain subjects for further scrutiny. Within animal models, a diverse therapeutic response was observed, with certain instances indicating complete tumor regression. Biodistribution data emphasized the nanoparticles' affinity towards particular organs, and the majority of hematological indicators aligned with normative standards. Conclusions: BSA-coated AuNPs manifest substantial promise as therapeutic tools in treating prostate cancer. The present research not only accentuates the nanoparticles' efficacy but also stresses the imperative of optimization to ascertain both selectivity and safety. Such findings illuminate a promising trajectory for avant-garde therapeutic modalities, holding substantial implications for public health advancements.

A simulation study on the radiosensitization properties of gold nanorods.

Objective. Gold nanorods (GNRs) have emerged as versatile nanoparticles with unique properties, holding promise in various modalities of cancer treatment through drug delivery and photothermal therapy. In the rapidly evolving field of nanoparticle radiosensitization (NPRS) for cancer therapy, this study assessed the potential of gold nanorods as radiosensitizing agents by quantifying the key features of NPRS, such as secondary electron emission and dose enhancement, using Monte Carlo simulations.Approach. Employing the TOPAS track structure code, we conducted a comprehensive evaluation of the radiosensitization behavior of spherical gold nanoparticles and gold nanorods. We systematically explored the impact of nanorod geometry (in particular size and aspect ratio) and orientation on secondary electron emission and deposited energy ratio, providing validated results against previously published simulations.Main results. Our findings demonstrate that gold nanorods exhibit comparable secondary electron emission to their spherical counterparts. Notably, nanorods with smaller surface-area-to-volume ratios (SA:V) and alignment with the incident photon beam proved to be more efficient radiosensitizing agents, showing superiority in emitted electron fluence. However, in the microscale, the deposited energy ratio (DER) was not markedly influenced by the SA:V of the nanorod. Additionally, our findings revealed that the geometry of gold nanoparticles has a more significant impact on the emission of M-shell Auger electrons (with energies below 3.5 keV) than on higher-energy electrons.Significance. This research investigated the radiosensitization properties of gold nanorods, positioning them as promising alternatives to the more conventionally studied spherical gold nanoparticles in the context of cancer research. With increasing interest in multimodal cancer therapy, our findings have the potential to contribute valuable insights into the perspective of gold nanorods as effective multipurpose agents for synergistic photothermal therapy and radiotherapy. Future directions may involve exploring alternative metallic nanorods as well as further optimizing the geometry and coating materials, opening new possibilities for more effective cancer treatments.

Gold(I) ion and the phosphine ligand are necessary for the anti-Toxoplasma gondii activity of auranofin.

Auranofin, an FDA-approved drug for rheumatoid arthritis, has emerged as a promising antiparasitic medication in recent years. The gold(I) ion in auranofin is postulated to be responsible for its antiparasitic activity. Notably, aurothiomalate and aurothioglucose also contain gold(I), and, like auranofin, they were previously used to treat rheumatoid arthritis. Whether they have antiparasitic activity remains to be elucidated. Herein, we demonstrated that auranofin and similar derivatives, but not aurothiomalate and aurothioglucose, inhibited the growth of Toxoplasma gondii in vitro. We found that auranofin affected the T. gondii biological cycle (lytic cycle) by inhibiting T. gondii's invasion and triggering its egress from the host cell. However, auranofin could not prevent parasite replication once T. gondii resided within the host. Auranofin treatment induced apoptosis in T. gondii parasites, as demonstrated by its reduced size and elevated phosphatidylserine externalization (PS). Notably, the gold from auranofin enters the cytoplasm of T. gondii, as demonstrated by scanning transmission electron microscopy-energy dispersive X-ray spectroscopy (STEM-EDS) and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS).IMPORTANCEToxoplasmosis, caused by Toxoplasma gondii, is a devastating disease affecting the brain and the eyes, frequently affecting immunocompromised individuals. Approximately 60 million people in the United States are already infected with T. gondii, representing a population at-risk of developing toxoplasmosis. Recent advances in treating cancer, autoimmune diseases, and organ transplants have contributed to this at-risk population's exponential growth. Paradoxically, treatments for toxoplasmosis have remained the same for more than 60 years, relying on medications well-known for their bone marrow toxicity and allergic reactions. Discovering new therapies is a priority, and repurposing FDA-approved drugs is an alternative approach to speed up drug discovery. Herein, we report the effect of auranofin, an FDA-approved drug, on the biological cycle of T. gondii and how both the phosphine ligand and the gold molecule determine the anti-parasitic activity of auranofin and other gold compounds. Our studies would contribute to the pipeline of candidate anti-T. gondii agents.